We have used in situ hybridization to investigate the modulation of expression of the immediate early genes (IEGs) c-fos, fos-B, zif/268 and CREM in rat brain following oral administration of saccharin, i.p. injection of LiCl, and conditioned taste aversion (CTA) training in which these stimuli are used as the conditioned stimulus (CS) and the unconditioned stimulus (UCS), respectively. Modulation of c-fos, zif/268 and CREM was detected in the NTS, PBN, hypothalamic PVN and central nucleus of the amygdala after the administration of the UCS but not the CS. Our data are consonant with the hypothesis that differential and combinatorial expression of IEGs plays a role in encoding the representation of LiCl-induced malaise in the brain.