Case series have suggested that heroin and cocaine users are at increased risk for renal failure, but the contribution of heroin and other addictive drugs to the incidence of end-stage renal disease (ESRD) in the general population remains unknown. To clarify this issue, we conducted a case-control study in the general population to examine associations between drug use and treated ESRD. Cases were 716 patients who started therapy for ESRD in 1991, identified through a regional registry. Controls were 361 persons of similar age (20 to 65 years) selected by random digit dialing. Main risk factors examined were the lifetime use of heroin, cocaine, and other addictive drugs, assessed by telephone interview. After adjustment for age, sex, race, socioeconomic status, and history of hypertension and diabetes, persons who had ever used heroin or other opiates (any amount) were at increased risk for ESRD (adjusted odds ratio, 19.1; 95% confidence interval, 1.7 to 208.7). After adjustment for the same sociodemographic and medical history variables, the use of cocaine or crack and psychedelic drugs was also associated with ESRD, but these associations could not be separated from the effects of heroin use.