Intro: Michelangelo narrates as we see a creepy laboratory similar to what we might see in a Frankenstein movie (the scene is in B&W to set the mood). Electricity surges from old turbines and generators, powering all sorts of strange equipment. Panning over we see a shadowy figure working at a table. Nearby we see Master Splinter strapped down to a gurney. Electricity arcs from some cables and surges all around the room.
Act 1: Open with a helicopter as it lands on a rooftop and leaves a barrel-sized high-tech cylinder and takes off. Around it are other choppers doing the same thing on nearby rooftops.
On the city streets we see a van stop at a manhole and several black-clad soldiers jump out. The men empty a large sack filled with dozens of can-sized cylinders, smaller versions of the ones being left by the choppers. The cylinders float through the sewers, separating into groups as they arrive at various intersections. Eventually a group of the devices make their way into a pool inside the Turtle Lair.
In a nearby helicopter, Bishop is informed that his “packages” have been delivered. With this information, he gives the command to activate the devices, and the cylinders begin emitting a high-pitched frequency throughout the sewers, driving the rats to the streets in effort to escape the sonic attack.
On the surface, the rooftop cylinders also begin to emit the frequency, filling the whole of New York City, above ground and below, with the sound.
As more and more rats flee the sewers, we see that Leatherhead has also fallen victim to the sonic attack - the pitch is driving him mad. In the Turtles' lair, Splinter is having the same response as other rats. Pain overwhelms the Sensei, so the Turtles take him and retreat to the Battle Shell. They blast into the streets trying to escape the noise - but there's no solace on the surface, either.
Bishop and his helicopter use sensors to trace the whereabouts of any mutant DNA and quickly home-in on the Battle Shell. The helicopter attacks, launching a barrage of missiles that the Battle Shell barley evades. Raph is driving the truck and manages to elude the vast majority of the projectiles, but the attack is relentless and one missile is headed directly at the Battle Shell.
Act 2: As the missile speeds down, it buries itself into the Battle Shell's roof, penetrating the armor. The weapon doesn’t explode, but it does release marbles filled with gas. As the gas overwhelms the Turtles, the truck comes to a screeching halt and the ninjas bail out of the vehicle. Unfortunately their efforts are too late and they are overcome by the gas and pass out on the street. Three black armored trucks arrive. Bishop’s men leap out of their vehicles and grab Master Splinter. Bishop orders them to leave no survivors, so the soldiers lift their guns and aim them at the Turtles. Just as it appears that the TMNT will be destroyed, Leatherhead crashes through a door and attacks the soldiers!
Cut to an abandoned subway station as the Turtles come to. As they awaken, the ninjas are met by Professor Honeycutt (in a temporary body made of salvaged parts) and Leatherhead. Knowing that Bishop has Splinter, our heroes realize that they can track him with the nearby subway car they stole from Bishop.
Inside Bishop’s lab, we see Splinter awaken. The Sensei is strapped to a gurney and Bishop stands over him. Bishop explains that he works for the Earth Protection League, an organization begun in 1870 under the sponsorship of President Grant (note that Bishop shows Master Splinter a photo of Grant signing the paperwork - and the man standing next to the President looks remarkably like Bishop). The organization's goal is to prevent hostile aliens from taking over the planet. To this end, the sinister operative informs Splinter that his rat DNA has been extremely beneficial to his work and has contributed greatly in the creation of a new form of superhuman that will protect the Earth. Splinter tells the man that he has no right to play god, and that the planet already has enough monsters. Bishop laughs and powers up his equipment. Electricty surges and engulfs another figure that's strapped to a gurney. Bishop cackles as he unveils his new creation, the first superhuman, a.k.a., the Slayer.
Act 3: By this time, the Turtles, Leatherhead, and Honeycutt have gotten the homing system on the subway car activated and the train is roaring towards its home destination. Bishop is alerted that the subway train is returning to his base, so he orders his men to welcome its arrival. Bishop then tells Splinter that he's lucky - he will be preserved for future exeriments. The man activates his machines and robotic arms lift splinter and deposit him into a stasis tube, that begins to fill with a vile, green liquid.
The TMNT and their allies arrive at Bishop’s lab where they are met by a group of armed guards. Our heroes attack and get the upper hand in the skirmish. The huge laboratory door begins to close, but Leatherhead holds it up long enough for the TMNT and Honeycutt to get inside. Once his friends are safe, Leatherhead drops the door and turns to fight the remaining guards.
Act 4: The TMNT rush into Bishop's inner sanctum. Bishop makes no move to meet their assault, but the Slayer intercedes and proves to be a formidable foe. As the Turtles and the Slayer do battle. The TMNT manage to get in a good hit that knocks off the Slayer’s protective helmet, revealing him to have a half-human, half-robotic face - with Bishop’s features! Bishop pauses to compliment the cyborg on its good looks and the the battle is renewed.
Leonardo orders Honeycutt to save his Master. The Professor uses Bishop's computer to free Splinter from the vat full of polymer. Unfortunately Bishop spots the robot at its work and uses a chain hook to rip off one of its arms - Honeycutt notes that this act was uncalled for. Splinter's tube falls from the grasp of the robotic arms, freeing the rodent ninja. The Sensei attacks Bishop while the Slayer continues to pummel the Turtles with an arsenal of moves and the ability to turn invisible.
Leo is able to throw the Slayer into a stasis tube full of the polymer. Honeycutt punches commands into the computer, sending an electrical surge into the vat that freezes the Slayer and allows the container be sealed, trapping the cyborg clone.
Splinter continues his fight with Bishop. In the skirmish, a turbine is damaged and explodes. Bishop and Splinter are both caught in the explosion and are sent flying. The man is impaled on an iron hook hanging from a chain. The detonation of the turbine has started several fires and a flood. More turbines explode and a torrent of water pours into the facility. Our heroes look away from the hanging Bishop for a second to assess the situation, and when they look back, the man is gone! Bishop calls out from a nearby ladder that the TMNT will pay for their actions and makes his escape. Our heroes run to the ladder and being climbing it as more turbines begin to explode, destroying the facility in fire and water. The flood waters carry off the stasis tube holding the Slayer.
The TMNT, Splinter and Professor Honeycutt climb the ladder to the streets, but there's no sign of their enemy.