Rats were exposed to high-dose intraperitoneal cocaine. Pretreatment with diazepam was found to be highly effective in reducing observed seizures from 90% to 0% and reducing the incidence of death from 85% to 10%. Furthermore, diazepam treatment after cocaine exposure was also effective in decreasing deaths, from 80% to 21%, even when given after the onset of seizures. Although diazepam pretreatment was shown to prevent clinically overt seizures, cortical EEGs in these rats demonstrated a continuum of convulsantlike electrical activity. Our study points to the protective effects of diazepam when given before or after cocaine exposure. Together, these data suggest that diazepam has significant efficacy against cocaine intoxication even though it does not totally suppress cocaine-induced cortical EEG seizure activity.