An animal model was sought that would mimic humans with regard to the dose-dependent pharmacokinetics of prednisolone. Four rabbits were each given 0.5 and 10 mg iv of prednisolone, and timed blood samples were obtained. Plasma prednisolone and prednisone concentrations were assayed by high-performance liquid chromatography, and protein binding was assessed using equilibrium dialysis at 37 degrees. Increases in the systemic clearance, volume of distribution at steady state, mean residence time (in three of four rabbits), and variance of residence time occurred as dose was increased. As in humans, prednisolone was partly converted to prednisone in the rabbit. Transcortin and albumin concentrations and their affinity constants for binding prednisolone were also similar to humans.