Deaths associated with injected street preparations of heroin increased substantially in the District of Columbia between April 1979 and December 1982. The 1981 population-based mortality rate (17.4 per 100,000) is possibly the highest ever reported. A case-control study based on toxicologic analyses of postmortem blood samples indicates that concentrations of both heroin and ethanol are substantial risk factors for heroin-related deaths. Analyses of the composition of street-level preparations of heroin and quarterly mortality indicate that the quantity of heroin in packages sold on the street, the price of heroin in these packages, and the quinine weight per package each predict deaths equally as well. An increase in the causal use of heroin in combination with ethanol and quinine is the probable cause of this epidemic.