Attempting yet again to "downsize" the Turtles [AKA revert them back to their lives as baby turtles, and therefore render them a threat no longer],
Krang sends Shredder, Rocksteady and Bebop to earth's surface to retrieve "compound X-7", a compound that will return the turtles to their pre-mutate state.
The two arrive at the nearby Tropotron laboratory, but they are unable to find "Compound X-7", in frustration, the two mutants destroy the lab, accidentally knocking over a barrel contain an unknown substance onto two garbage men in the process.
Tipped off by April, the turtles arrive at Tropotron to break up the rampage, after a skirmish, Shredder and his two underlings retreat.
Meanwhile, the once-ordinary garbage men have now found themselves mutated into horrible apparitions, they are repelled by their appearance and go nuts.
Whoever did this foul deed to them, after watching a misinterpreted channel six news broadcast blaming the turtles for the lab break-in, the new mutants come to the conclusion that they green machine are responsible for their predicament they name themselves Muck-man and Joe Eye-Ball and venture forth to exact vengeance.
Muck Man and Eyeball don't have to search long to find the tmnt, and they do battle with them. The battle weakens the Turtles greatly, and they are unable to prevent their adversaries from carting April and Irma [who had chosen the wrong place at the wrong time in investigating the mystery of the missing garbage men] off.
Recovering at their lair, Donatello discovers the reason he and his bros were weakened by Muck man and Eyeball, and begins work on a cure, but first he must return to Tropotron and obtain a sample of the same mutatagen which gave birth to their current adversaries in the first place.
The remaining turtles and Splinter embark on a mission to rescue April and Irma.
After gaining the mutagen, Donatello reunites with his bros just as they are again confronted by Muck man and Joe Eyeball, who now have Shredder, rolcksteady and Bepop on their side!
Before they can even attempt to attack, the turtles are again weakened by the mere presence of Muckman and Eyeball, Splinter is captured by Shredder, who makes preparations to return to the Technodrome, leaving the tmnt to the tender mercies of his new allies.
Luckily April and Irma are able to bring muckman and eyeball to the side of good once again when they show the duo video footage of Shredder's earlier attack on Tropotron, and spilling the mutagen barrels onto two garbage men: Muckman and eyeball have found out the truth, and they ain't happy.
Muckman and Eyeball help Donatello create the antidote, which prevents the TMNT from being affected by the mutagenic radiation emitted from the two mutates, the fully recovered heroes in a half shell battle Shredder and rescue Splinter.