The authors studied the use of heroin, marijuana, and cocaine before the onset of a first seizure in 308 patients with seizures and 294 controls at Harlem Hospital Center, New York City, between 1981 and 1984. Heroin use, both past and present, appeared to be a risk factor for all first seizures (adjusted odds ratio = 2.80, 95% confidence interval (CI) 1.53-5.74). For unprovoked seizures, the adjusted odds ratio was 2.58 (95% CI 1.36-4.90) for ever heroin use and 4.70 (95% CI 0.86-25.78) for heroin use within 24 hours of hospitalization. For provoked seizures, respective adjusted odds ratios were 3.65 (95% CI 1.54-8.65) and 27.74 (95% CI 3.57-215.52). Marijuana use appeared to be a protective factor against first seizures in men. For men with unprovoked seizures, the adjusted odds ratio was 0.42 (95% CI 0.22-0.82) for ever marijuana use and 0.36 (95% CI 0.18-0.74) for marijuana use within 90 days of hospitalization. For men with provoked seizures, respective adjusted odds ratios were 1.03 (95% CI 0.36-2.89) and 0.18 (95% CI 0.04-0.84). Cocaine use, while common among study subjects, was not shown to be a significant risk factor either for all first seizures or for subgroups of seizures, regardless of the time of last use. The authors conclude that heroin use is a risk factor and marijuana use a protective factor for new-onset seizures.