The effects of aspirin, cyclophosphamide, and dexamethasone on secondary herpes simplex uveitis were studied in rabbits. Neither daily treatment with aspirin (rectal suppositories, 650 mg begun 24 hours before challenge) nor cyclophosphamide injections every two days (80 mg begun eight days before challenge) had any effect on the severity of the uveitis, on the rise in intraocular pressure (IOP), or on the host's immune responses. As in the control animals, infectious herpes simplex virus (HSV) could not be isolated from iris tissues of either aspirin- or cyclophosphamide-treated rabbits. On the other hand, twice-daily treatment with topical dexamethasone (0.1% drops begun 24 hours before challenge) lessened the severity of the uveitis appreciably and suppressed the rise in IOP, but iris tissues yielded infectious HSV in two of ten eyes. Although the dexamethasone had no effect on the neutralizing-antibody or macrophage migration inhibition factor, it markedly suppressed the chemotactic activity of the aqueous humor for both polymorphonuclear leukocytes and macrophages.