The effects of a combined use of steroidal and nonsteroidal anti-inflammatory topical drugs on uveitis were studied. Uveitis was induced by intravenous injection of E. coli endotoxin (10 micrograms/kg) in pigmented rabbits. A solution of 0.5% indomethacin (IM) and/or 0.1% betamethasone (BM) was instilled 4 times: at 1 hour before and at 0, 2 and 4 hours after the endotoxin injection. The aqueous protein was quantified by laser flare-cell measurements hourly after the injection. The prostaglandin E2 concentration was assayed and venous leukocytes and thrombocytes were counted 5 hours after the endotoxin injection. The aqueous protein reached a peak concentration (27 mg/mL) about 4 hours after the endotoxin injection. IM, BM and a combination of IM and BM (IM + BM) inhibited the aqueous protein rise by 17, 63 and 94%, respectively. IM, BM and IM + BM almost completely inhibited the increase of aqueous prostaglandin E2. IM + BM inhibited both leukocytopenia and thrombocytopenia. IM alone had no effect on these counts, and BM alone inhibited leukocytopenia only. The data suggest that the combined use of topical IM and BM is more useful for the therapy of endotoxin-induced uveitis than each drug alone. The inhibitory effects may be synergistic, probably acting on unknown mediators which may be derived from the systemic circulation.