The pharmacokinetics of a 40-mg intravenous dose of prednisolone were determined in 10 steroid-dependent asthmatic children with highly variable prednisone requirements (5 mg every other day to 40 mg a day). Concentrations of prednisolone and cortisol in plasma over a 24-hr test period were measured by high-performance liquid chromatography. Eosinophil concentrations and the concentration-dependent protein binding of prednisolone were also determined. The mean (+/-SD) apparent half-life of prednisolone in these children was 2.5 +/- 0.5 hr. The mean total volume of distribution was 52.8 +/- 14.5 L/1.73 m2 and mean plasma clearance was 246 +/- 62 ml/min/1.73 m2. These pharmacokinetic parameters, as well as the protein binding and eosinopenic response, were similar to values from healthy and steroid-dependent asthmatic adults. The data were also similar in both responsive and relatively resistant patients. The pharmacokinetics and protein binding of prednisolone are not responsible for the highly variable prednisone requirement and clinical response of these children to prednisone therapy.