The efficacy of diazepam, haloperidol, propranolol, and yohimbine in antagonizing the toxic manifestations of d-amphetamine were studied in rats. In the control group of animals given 75 mg/kg intraperitoneal (ip) d-amphetamine, 95% developed seizures, and 100% died in mean times of 12.6 +/- 1.0 and 50.1 +/- 5.9 minutes, respectively. Significant protection against d-amphetamine-induced death was afforded by pretreatment with haloperidol (1.0 to 20.0 mg/kg) or propranolol (20.0 to 30.0 mg/kg). Diazepam (5.0 to 10.0 mg/kg) significantly reduced the incidence of clinically overt seizures but offered no protection against death. Yohimbine (2.5 to 10.0 mg/kg) was ineffective in preventing either seizures or death. When haloperidol (1.0 mg/kg) was administered in combination with diazepam (2.0 mg/kg), the incidence of death was no different than if haloperidol were given alone. In combination, haloperidol (1.0 mg/kg) and propranolol (10.0 mg/kg) reduced death more than either agent alone. These data support a protective role of haloperidol or propranolol in the treatment of d-amphetamine intoxication and show no protection with diazepam or yohimbine.