The anesthetic requirements of chronic alcoholics for induction of anesthesia with thiopental were investigated using an electroencephalographic (EEG) measure of thiopental's CNS drug effect and pharmacodynamic modeling to relate thiopental serum concentrations to drug effect. Eleven patients with a history of excessive alcohol intake were studied from an inpatient alcohol rehabilitation program and compared with nine control patients or volunteers who were social drinkers. The alcoholic population had consumed ethanol 9–17 days prior to the study. They had no evidence of acute intoxication or acute withdrawal at the time of the study. Five of the 11 alcoholic patients were restudied after 1 month of abstinence from alcohol consumption. Each study consisted of a thiopental infusion until EEG burst suppression (1–3s of isoelectric signal) was achieved. Timed arterial and then venous blood samples were obtained for measurement of thiopental serum concentrations for up to 36 h. Pharmacokinetic differences between groups were analyzed using a three-compartment model. Power spectral analysis of the EEG allowed determination of spectral edge frequency. An inhibitory sigmoid Emaxpharmacodynamic model combined with an effect compartment was used to analyze concentration-response relationships and to provide an estimate of brain sensitivity to thiopental in the study populations. The thiopental anesthetic dose requirement using the EEG was not different between alcoholics and nonalcoholics. The mean dose requirement (± SD) of alcoholics was 823 ± 246 mg and the mean dose requirement of nonalcoholics was 733 ± 218 mg. There were no differences in thiopental pharmacokinetic and pharmacodynamic parameters between alcoholics and nonalcoholics. In the subgroup of five alcoholics who were studied approximately 1 month later, thiopental dose requirement, pharmacokinetics, and pharmacodynamics had not changed. These findings suggest that thiopental induction doses should not be routinely increased in chronic alcoholic patients.