The effect of dexamethasone in two regimens on retinal photic injury was studied in Lewis albino rats that were exposed to 24 hr of continuous green fluorescent light. Under regimen 1, dexamethasone was given at a daily dosage of 1 mg kg-1 for 8 days, starting 6 days before light exposure. Under regimen 2, dexamethasone was given at the same daily dosage for 3 days, started 1 day before light exposure. Pathologic study of the light-exposed retina, morphometric evaluation of the photoreceptor cell loss, cell counts of the macrophages in the subretinal space, and measurements of rhodopsin levels were undertaken in the dexamethasone-treated and control retinas at various times. The administration of dexamethasone in both regimens did not produce pathologic changes in the retina before light exposure, but rhodopsin levels were significantly lowered in both treated groups when compared to corresponding vehicle treated control animals. Under regimen 1, at 6 hr after light exposure, both the treated and the control groups showed comparable loss of photoreceptor cells, degeneration of the photoreceptor elements and retinal pigment epithelium, but a significantly lowered level of rhodopsin in the treated group was noted. At 6 days after exposure, the outer nuclear layer thickness, and the outer and inner segments showed significant preservation in the treated group. Also in the treated group, the number of macrophages was significantly reduced and the retinal pigment epithelial (RPE) vacuolation was markedly less. However, there was no difference in rhodopsin levels. At 14 days after exposure, the outer nuclear layer thickness and rhodopsin levels of the treated rats had significantly higher values than the controls. Under regimen 2, however, at 6 days after exposure, an ameliorative effect in the RPE was observed but there were no differences of rhodopsin levels, the outer nuclear thickness and number of macrophages between the treated and control groups. Regimen 1 was associated with a significantly higher retinal level of dexamethasone when compared with regimen 2. The ameliorative effect of dexamethasone on rat retinal photic injury may be through inhibition of lipid peroxidation, in which a high retinal level of the steroid is required.