In most subcortical visual centers in normal mice maintained for a period in the dark, very few neurons express fos-like immunoreactivity (FLI), most likely reflecting c-fos expression, but if an animal is exposed to a flashing light, there is transient increase in the number of FLI-expressing cells. In dark-maintained retinal degeneration (rd) mice, with an inherited photoreceptor defect, numbers of FLI-positive cells, identified immunohistochemically, are anomalously elevated in the superior colliculus (SC) and lateral geniculate nucleus (LGN). Eye removal largely prevents the elevated counts. The difference in number of FLI-positive cells in the SC of rd mice and nondystrophic controls is highly significant (p<0.001). Because we have previously found a similar phenomenon in Royal College of Surgeons (RCS) rats, in which photoreceptor loss is caused by a retinal pigment cell defect, it argues for an effect related to photoreceptor loss rather than its cause.