Cells within the auditory brainstem of cat that respond to sound by producing the transcription factor Fos or related proteins were identified by immunostaining with antisera against Fos and Zif/268. Within the cochlear nucleus, all antisera showed similar staining patterns, however, in the superior olive and inferior colliculus, staining patterns differed between antisera. Immunostained cells were characterized by their size, location, by the presence of perisomatic terminals that immunostained for glutamate decarboxylase or synaptophysin, or by electron microscopy. Most cell classes were not immunopositive. In the ventral cochlear nucleus, roughly 99% of Fos-positive cells had few perisomatic terminals. Within the superior olivary complex (SOC), the majority of immunopositive cells had few perisomatic terminals. Lateral olivocochlear cells were identified as Fos positive by their size, location, lack of perisomatic terminals, and positive costaining for acetylcholinesterase as evidenced by a novel reaction product. This report appears to be the first demonstration of these cells responding to sound stimulation. Within the inferior colliculus, bands of positive cells produced by tonal stimulation extended from the central nucleus throughout the dorsal cortex and the posterior pericentral region, a finding unexpected on the basis of previous electrophysiological recordings and anatomical studies of ascending inputs to the colliculus. Approximately 35% of Fos-positive cells in the inferior colliculus had plentiful perisomatic terminals. Results demonstrate a high degree of specificity of auditory cell types that respond to sound by producing Fos-like proteins and show that previously intractable physiological questions can be addressed by assaying for sound-induced production of these antigens. (C) 1995 Wiley-Liss, Inc.