In a prospective, uncontrolled study, 62 alcoholic patients received IV phenobarbital (IV-PB) to treat the alcohol withdrawal (AW) syndrome. Initially 260 mg of IV-PB were administered followed by 130 mg every 30 minutes to an end point of light sedation. A mean loading dose of 598 (+/- 192) mg of IV-PB resulted in a mean increase in the serum PB level of 13.9 (+/- 4.7) microgram/mL. Thus, the serum PB level rose 1.65 micrograms/mL for each mg/kg of IV-PB administered to these adult patients in AW. Forty-six of 48 tremulous patients (96%) showed improvement in their AW tremors. None of the 38 patients who presented with AW seizures had another convulsion during a mean observation period of three hours and 47 minutes. Transient ataxia or over-sedation occurred in three of 62 patients (5%) and was exacerbated by concurrent ethanol, diazepam, or phenytoin (six of 17), who were excluded from the study. We conclude that IV-PB is a safe and efficacious therapy for mild to moderate AWS, and IV-PB may prevent AW seizures.