In a recent study, we reported that bFGF content and mRNA expression levels are elevated in degenerating photoreceptors in the rd mouse retina as compared to the levels in photoreceptors in age matched normal retinas (Gao and Hollyfield, 1995). To determine whether bFGF up-regulation is a general feature of degenerating photoreceptors, bFGF expression was examined with in situ hybridization in several rodent models with retinal degeneration: (a) the normal mouse retina in which cGMP metabolism had been disrupted pharmacologically using an inhibitor of phosphodiesterase or an analog of cGMP, (b) the rds mouse with an inherited photoreceptor degeneration that does not involve alterations in cGMP metabolism, (c) light-damaged BALB/c mice subjected to bright constant light, and (d) light-stressed albino rats subjected to bright cyclic light. In each of these models, we observed dramatic up-regulation of bFGF gene expression in photoreceptors, although the relative levels varied among the different models and followed different temporal patterns. We conclude that increased expression of bFGF in photoreceptors during their degeneration is a general phenomenon occurring in rd, rds, light-damaging and light-stressing conditions. These observations indicate that bFGF can be up-regulated by a variety of photoreceptor insults. We speculate that endogenous bFGF may function as a photoreceptor protection/rescue factor that is activated in response to photoreceptor stress.