Interleukin-1beta (IL1beta) and tumor necrosis factor-alpha (TNFalpha) are involved in several physiological functions regulated by brain. The current studies were performed to determine whether a diurnal rhythm of IL1beta and TNFalpha mRNAs, determined by real time RT-PCR, existed in specific brain regions linked to the functions of these cytokines. Rats were sacrificed 2 h after light onset (AM) and 1 h prior to dark onset (PM). IL1beta mRNA levels in the AM were significantly higher than those obtained from rats sacrificed in the PM in the prefrontal cortex, parietal cortex, amygdala/piriform cortex, ventral hippocampus, hypothalamus, nucleus tractus solitarius, and nucleus accumbens, but not in the dorsal hippocampus. Time-of-day differences in TNFalpha mRNA levels were observed in all these brain regions. These results support the hypothesis that TNFalpha and IL1beta have physiological roles within the brain.