Male albino (Sprague Dawley) and pigmented (Norwegian Brown) rats received 1% 2,5-hexanediol (H) in their drinking water for 5 or 8 weeks, respectively. The rats were housed either in 12 h light (average 30 cd/cm2 inside cage) and 12 h darkness (group LH) or in total darkness (group DH). Two control groups (Light only, LC; Darkness only, DC) were studied in parallel under identical conditions. The animals were sacrificed at the end of H exposure or after an ensuing 13-week period without H but under the same lighting conditions. The retinas of albino rats in the LH group showed a reduction (compared to the LC, DH and DC groups) in the number of nuclei per unit area of the outer nuclear layer (ONL; p < 0.05) and degeneration of the outer segment and the inner segment layers (photoreceptor cells). A less pronounced loss of nuclei was seen in the LC group. No decrease in the number of nuclei, or signs of degeneration, were demonstrated in the albino DH or DC groups. Thirteen weeks after exposure to H, the albino LH rats had lost about 50% of the nuclei in the ONL (p < 0.05) and the outer plexiform layer (OPL) had almost disappeared. At the corresponding time, in the pigmented rats the LH and DH groups differed from the LC and DC groups. The degenerative process resulted in no inflammatory changes in the retina. The results imply an interaction exceeding simple summation after exposure to light and H, in destroying photoreceptors and OPL (p < 0.001) in albino rats.(ABSTRACT TRUNCATED AT 250 WORDS)