Data from a prospective study of the clinical course in 223 patients with systemic lupus erythematosus followed for 655 patient-years were analyzed by computer to determine the influence on frequency of infection of 1) corticosteroid dose; 2) azathioprine; 3) active disease, measured by new disease exacerbations, elevated ESR, hypocomplementemia, active urinary sediment, and proteinuria; 4) uremia; and 5) leukopenia. The frequency of all infections, and of bacterial and opportunistic infections specifically, increased progressively with increasing steroid dose. Azathioprine use, independent of steroid dose, did not account for an increased risk of bacterial, opportunistic, or nonspecific viral infections. Leukopenia did not predispose to infection, except possibly when associated with azathioprine-induced bone marrow suppression. Active renal disease, especially when manifested by abnormal urine sediment, was associated with an increase in infection frequency.