The pharmacokinetics and protein binding of prednisolone have been compared in 6 uremic patients and 6 healthy controls after intravenous injection of 20 mg prednisolone. The uremic patients had a 53% longer elimination half-time (p less than 0.01) and a 34% larger area under the time-concentration curve (AUC) (p less than 0.05) of total prednisolone than the controls. The total body clearance of total prednisolone was 26% lower and of free prednisolone 40% lower in the uremic patients than in the controls (p less than 0.01). The volume of distribution at steady state was 17% larger in the patients than in the controls, but the difference was not statistically significant. The protein binding of prednisolone was decreased in the patients, the proportion of free prednisolone being 26% higher than in the controls (p less than 0.05). The amount of free prednisolone, expressed as the AUC of free prednisolone, was 67% larger in the patients than in the controls (p less than 0.01). These results indicate that uremic patients taking prednisolone may be more prone to develop glucocorticoid side-effects because of higher concentration of free, biologically active prednisolone, secondary to a reduced rate of elimination and a decreased serum protein binding of prednisolone.