The pharmacokinetics and protein binding of prednisolone were studied in 7 patients before and after 3 weeks of rifampicin therapy. The elimination half-time for prednisolone decreased by 45 +/- 8.1% (p less than 0.01), and the total body clearance of prednisolone increased by 91 +/- 26% (p less than 0.01). The area under the time-concentration curve (AUC) of total (free plus protein-bound) prednisolone decreased by 48 +/- 7.3% (p less than 0.01) and of free, unbound prednisolone by 57 +/- 9.8% (p less than 0.01). The reduction in AUC was greater for free than for total prednisolone (p less than 0.05) mainly due to the non-linear nature of prednisolone protein binding. There was no significant change in the volume of distribution. Because of the marked reduction in total and especially free prednisolone, the dosage should be adjusted accordingly if prednisolone and rifampicin are prescribed concomitantly.