Ethanol or drug use may increase the risk of fire-related injury or death. This study was performed to quantify the role of substance abuse in fatal fires occurring in New Jersey over a 7-year period. Records of all the fatalities of fire reported to the State Medical Examiners Office between 1985 and 1991 were retrospectively examined. Blood assay results for ethanol were positive in 215 of the 727 (29.5%) fatalities of fire tested. For this group, the mean blood-ethanol level was 193.9 mg/dl. Blood or urine assay results for substances of abuse were positive in 78 of the 534 (14.6%) fatalities tested. The most commonly detected illicit substances were cocaine, benzodiazepines, barbiturates, and cannabinoids. The test results were positive for both ethanol and drug use in 36 victims. Forty percent of all the fatalities of fire were aged younger than 11 or older than 70. In contradistinction, 75% of drug-positive fatalities of fire and 58% of ethanol-positive fatalities of fire were between the ages of 21 and 50, suggesting that inebriation may impair the ability to escape from fire. Substance abusers in middle life are a previously unrecognized group at higher risk of injury or death in a fire.