Phenobarbital (0.03 to 0.04 mg/kg/min) was infused intravenously in 7 patients with clinical hypnosedative withdrawal reaction until patients slept but were arousable. The infusion time to reach this clinical end point was 7.8 +/- 1.1 hr (mean +/- SEM), the total dose was 992 +/- 144 mg, and the peak serum phenobarbital concentration was 26.1 +/- 5.1 micrograms/ml. A user of minimal hypnosedatives required 54% less phenobarbital and 65% lower concentration than any of the abusers to reach an equivalent state of intoxication. The mean serum half-life (t 1/2) was 57.5 +/- 4.9 hr for hypnosedative abusers and 86 +/- 3 hr for 8 normal volunteers (p less than 0.001). Only the patient with the shortest t 1/2 (36.4 hr) required oral phenobarbital supplements to prevent withdrawal symptoms. Dosage supplements required can be calculated from the postinfusion rate of fall of serum phenobarbital. Slow infusion of large amounts of phenobarbital provides a safe, efficacious single-dose treatment.