"Ren's Brain" is the final segment to credit John Kricfalusi, Chris Reccardi and Richard Pursel. The script was written before Kricfalusi's termination from the series in 1992.
The building Ren's brain works in is called "Stabco", referencing a nickname given to ex-Spumco members that still worked on the show after John Kricfalusi was fired.
Ren's brain yelling "YOU EEDIOTS!" in the end of the episode is taken directly from "Sven Hoek (1992)", which was said by John Kricfalusi himself when working on the episode from season two.
Ren's Brain along with Lair of the Lummox (1994) and Stimpy's Cartoon Show (1994) are the last three episodes written by John Kricfalusi after being fired in September 1992.
When Ren is just a brain, his blood vessel arms are red, but when he comes home, they temporarily turn pink.