Thiopental and pentobarbital have been used in high doses to protect the brain from injury following hypoxia or to reduce intracranial pressure. This study was performed to determine whether these barbiturates differ in cardiovascular effects when present in plasma concentrations that produce equivalent CNS effects. The effects of thiopental and pentobarbital on heart rate, stroke volume/kg, cardiac output/kg, systemic vascular resistance, mean arterial pressure, and central venous pressure were statistically indistinguishable at plasma concentrations of each barbiturate ranging from 50% to 100% of their concentration producing EEG silence. Three of the seven dogs given thiopental developed ventricular bigeminy at plasma concentrations ranging from 45% to 65% of their concentration producing EEG silence. Lidocaine (1.4-2.0 mg/kg intravenously) reversed the bigeminy to sinus rhythm. When given more than the amount needed to produce a flat EEG, five of the seven dogs given thiopental died, but all dogs given pentobarbital survived. Pentobarbital may be a better choice than thiopental when large doses are indicated.