The plasma levels of hexobarbital in humans were determined during and after a 30-min or 60-min zero-order intravenous infusion. Hexobarbital kinetics could be described by conceiving the body to exhibit two compartments. The plasma concentrations were fitted to the postinfusion equation and the parameters intrinsic to the two-compartment open model were estimated. The elimination half-life varied considerably among the 14 individuals (160-441-min), which could mainly be explained by the greatly varying metabolic clearance of the compound (123-360 ml/min). The apparent volume of distribution per kilogram of body weight was relatively constant (1.10 plus or minus 0.12 liters/kg).