Daily rhythms in the mammalian retina are regulated by an endogenous circadian clock. Previously it was found that neuronal elements of the rat retina respond to light:dark (L:D) transitions with cell-specific changes in expression of the c-fos gene. Using a pan-Fos antibody to probe Western blots of rat retina, we have now shown that darkness is associated with a 60-fold increase in c-Fos protein, whereas levels of FosB and Fos-related antigens are invariant. The induction of c-Fos exhibits circadian dependency; accumulation of c-Fos protein was significantly enhanced, by a factor of 2.5-fold, when darkness onset was coincident with the established L:D transition. c-Fos exhibited only a low amplitude circadian rhythm in the absence of L:D cycles. Similar results were obtained for another immediate early gene (IEG) protein, Egr-1. These findings show that IEG induction in the rodent retina exhibits circadian clock dependency.