The glial intermediate filament protein (GFAP) gene is not normally expressed by retinal Müller cells but it is transcriptionally activated following photoreceptor degeneration. In the present study, we have examined the relationship between progressive photoreceptor loss and changes in GFAP gene activity in Müller cells. In albino mice with light-induced photoreceptor degeneration, GFAP level was strongly elevated after 2 weeks. GFAP level remained high even after 3 months in light. In situ hybridization studies showed that GFAP transcripts were quite sparse in the first week but increased dramatically after 2 weeks of light exposure. After 4 weeks in constant light, however, little GFAP mRNA was detected in Müller cells. RNA blotting also showed that there was an approximately 20-fold increase in GFAP mRNA content at 2 weeks; but at 4 weeks, the RNA content fell to about four-fold higher than the basal level. These results show that GFAP level remains high long after its synthesis, probably as a consequence of low GFAP turnover in the Müller cell cytoskeleton, while GFAP mRNA level rises and declines rapidly due to transient activation of the GFAP gene in Müller cells.