To ascertain the incidence of infections in intravenous users of illicit drugs, we performed a retrospective study of 270 intravenous drug users (IVDUs) and 562 controls who did not use drugs over a seven-year period from 1978-1985. IVDUs had an increased overall incidence of infections (P <0.00l) compared to controls, which was explained to a large degree by an increased incidence of hepatitis. Endocarditis and disseminated gonococcal infection were seen with increased frequency in IVDUs (P <0.05), but abscess and cellulitis were not. Neither acquired immunodeficiency syndrome (AIDS), tuberculosis, Pneumocystis pneumonia, nor disseminated viral or fungal infection were seen in IVDUs or controls. Heroin users, but not other IVDUs, had an increased incidence of infections not thought to be associated with needle use, suggesting impaired immunity. This study demonstrates that IVDUs have an increased incidence of infection compared to control subjects, but the kinds of infections have changed substantially over the past two decades. The presence of opportunistic pathogens in these patients should suggest concurrent infection with human immunodeficiency virus (HIV).