Systemic vitamin A palmitate at three dosage levels was evaluated for its effect on experimental herpes simplex virus (HSV) keratitis in corticosteroid-treated rabbits. High-dose vitamin A palmitate reduced the severity of herpetic keratitis, but the low or moderate doses did not, and none of the vitamin A treatments affected virus recovery. Vitamin A treatment, however, produced substantial weight loss in uninfected rabbits and in corticosteroid-treated, HSV-infected rabbits. Steroid treatment alone significantly increased the antibody response to HSV, but this effect was not enhanced by vitamin A. The slight beneficial effect on HSV keratitis could be attributed to the known effect of vitamin A on promoting epithelial healing rather than an enhancement of immunity. For this purpose, local application of vitamin A may be just as effective and much less toxic than administration for systemic effect.