Fos, the product of the proto-oncogene c-fos, is a nuclear phosphoprotein thought to participate in transcriptional regulation of target genes. To explore the synaptic induction of Fos and related proteins in vivo, Fos immunohistochemistry was performed in the rabbit retina. Dark-adapted retinas had virtually no Fos immunostaining. Retinas of dark-adapted rabbits that were exposed to 3 Hz diffuse flashing white light for 1 h and sacrificed 2 h later displayed nuclear Fos immunostaining in a minority of neurons. These included presumptive amacrine cells of the inner nuclear layer and either displaced amacrine cells or ganglion cells of the ganglion cells of the ganglion cell layer. Therefore, Fos or a related antigen is expressed in a subset of retinal neurons in response to light and is presumably involved in regulating gene expression of these cells to respond to alterations in synaptic activity.