The distribution and levels of c-fos expression in response to changes in the light/dark cycle were examined in rat retina by in situ hybridization histochemistry. Under a 12 hr light: 12 hr dark cycle (LD 12:12), c-fos mRNA levels in the inner nuclear layer and the ganglion cell layer increased transiently for 30 min immediately following the onset of the light period, whereas in the outer nuclear layer, c-fos mRNA expression was observed throughout the dark period. During a period of extended darkness following the dark period of LD 12:12, c-fos mRNA levels in the outer nuclear layer remained cyclic--low during the day and higher during the night--suggesting an endogenously generated rhythm. Furthermore, since a 30 min pulse of light during the dark period decreased c-fos expression in the outer nuclear layer, whereas a similar pulse of darkness during the light period resulted in an increase, environmental light/dark cues are also suggested to influence c-fos gene expression.