Most of the Pinky and the Brain episodes occur in the present time at Acme Labs, located in some large American metropolitan city, presumably Los Angeles as to tie in with Animaniacs and the Warner Brothers studio lot. However, several episodes took place in historical times, with Pinky and the Brain under the laboratory care of some scientifically-minded person, including Merlin, H.G. Wells and Ivan Pavlov. The bulk of every episode involves one of Brain's plans for world domination with Pinky's assistance, and the ultimate failure of that plan. One centers on his rival Snowball's plan to take over the world using Microsponge. Another episode features Brain's single day where he tries to do anything but take over the world, but in the end, a group of people vote that he should take over the world on the one day he is not wanting to. There is very little continuity on the show outside of the common fixtures of the mice, though some plans for world domination from early episodes are subsequently referred to in later seasons (for example, Brain's "human suit" used in "Win Big" reappears when Brain faces against Snowball in "Snowball".)
Both Pinky and the Brain, white mice kept as part of Acme Labs' experimentation have undergone significant genetic alteration; as per the show's title lyrics, "their genes have been spliced" which gives the two mice amplified intelligence over that of a typical mouse, the ability to talk to humans, and anthropomorphism. "Project B.R.A.I.N." suggests that the gene splicing occurred on September 9, 1995, coincident to the first full episode of Pinky and the Brain. The episode "Brainwashed" states that the gene splicing was done by Dr. Mordough, along with Snowball the hamster and Precious the cat, using the Acme "Gene Splicer and Bagel Warmer".
Although Pinky and the Brain plan to conquer the earth, they do not show much antagonism; in a Christmas special Pinky even wrote to Santa that Brain had the world's best interests at heart.
