Heroin-related overdose is the single largest cause of accidental death in San Francisco. We examined demographic, location, nontoxicological, and toxicological characteristics of opiate overdose deaths in San Francisco, California. Medical examiner's case files for every opioid-positive death from July 1, 1997, to June 30, 2000, were reviewed and classified as overdose deaths or other. Demographic variables were compared to two street-based studies of heroin users and to census data. From 1997 to 2000, of all heroin-related overdoses in San Francisco, 47% occurred in low-income residential hotels; 36% occurred in one small central area of the city. In 68% of deaths, the victim was reportedly alone. When others were present between last ingestion of heroin and death, appropriate responses were rare. In three cases, police arrested the person who called emergency services or others present on the scene. We recommend the development of overdose response training targeted at heroin users and those close to them, including the staff of residential hotels.