The death rate from asthma has been increasing in the U.S. and in many other countries and is considered unacceptably high. There is little information as to circumstances surrounding these fatalities that would lead to effective interventions to prevent deaths. In this study, cases of asthma deaths from the Office of the Medical Examiner in Cook County, (Chicago), Illinois were identified in subjects 45 years of age or less who died from asthma. We reviewed clinical information surrounding the deaths, contacted surviving kin, friends, or informants, and reviewed autopsy findings and toxicologic results. Deaths were classified as (1) from asthma, (2) probably from asthma, (3) of indeterminate cause, and (4) coincidental to but not from asthma. From 39 cases from one pathologist's cases of asthma deaths during 1985-1992, deaths were from or probably from asthma in 22/39 (56.4%) of cases. Eight (20.5%) cases were classified as indeterminate because of a positive or unknown asthma prodrome but in which toxicologic results were positive. Nine (23.1%) cases were classified as death coincidental to but not from asthma because of the absence of a prodrome of increased symptoms associated with positive toxicologic results. Overall from 23 cases where some toxicologic testing was performed, 14 (60.8%) were positive, individually or in combination, for cocaine, benzoylecgonine (cocaine metabolite), codeine. phencyclidine (animal tranquilizer), morphine, methadone, and ethanol (>0.8 g/L). Out-of-hospital asthma deaths in 39 subjects were complicated by a high incidence of illicit drug use, lack of identifiable managing physicians, lack of antiinflammatory medications, and in some cases not having been examined by a physician in the past year. Concomitant use of cocaine and bronchodilators may be especially dangerous in patients with asthma.