We performed a nonrandomized clinical trial comparing the ocular and systemic efficacy of cytotoxic immunosuppression with steroidal and nonsteroidal anti-inflammatory therapy in the care of 34 patients with rheumatoid arthritis who developed peripheral ulcerative keratitis and/or necrotizing scleritis. Nine of the 17 patients managed with conventional therapy died of a vascular-related event during the ten-year period of the study. In 13 of the 17 patients, the ocular inflammatory process progressed, and in 5 patients extraocular, although nonlethal, vasculitic lesions developed. One of 17 patients treated with long-term immunosuppressive therapy died during the ten-year follow-up period, and this death occurred after cytotoxic therapy was withdrawn. None of the patients on immunosuppressive regimens developed extraocular vasculitis while taking the drug, and none had progression of the ocular destructive lesion. The results of this study emphasize that the eye is a sensitive indicator for potentially lethal occult systemic vasculitis in patients with rheumatoid arthritis who develop peripheral ulcerative keratitis or necrotizing scleritis. Our mortality data strongly suggest that the use of cytotoxic drugs may alter favorably the general as well as the ocular prognosis in these patients.