The two-process model of sleep regulation posits that a homeostatic drive to sleep, referred to as Process S, increases with time spent awake. The purpose of this study was to evaluate whether immediate early gene (IEG) expression increases in the brain in proportion to time spent awake, when Process S would be expected to increase. Rats were deprived of sleep by cage tapping, cage rotation and gentle handling beginning at light onset for 45 minutes, 3 hours or 6 hours. At the end of the deprivation periods, deprived animals and an equal number of controls were decapitated, the brains dissected into subregions and frozen. Northern blots were prepared from cortex, thalamus, cerebellum, pons and hypothalamus and hybridized with cDNA probes to five IEG mRNAs; c-fos, c-jun, junB, NGFI-A and NGFI-B. Basal levels of c-fos mRNA were detectable in all brain regions from all animals. Sleep-deprived animals showed higher expression of c-fos mRNA than control animals following 45 minutes and 6 hours of sleep deprivation in all brain regions examined, with the greatest increases observed in the cerebellum. Surprisingly, only the pons and cerebellum showed clear increases at the 3-hour timepoint. In contrast to c-fos, c-jun mRNA was essentially invariant among the animals while junB mRNA was inconsistently elevated. The expression of NGFI-A and NGFI-B was similar to the c-fos pattern but of lesser magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)