The effect of plasma exchange on the pharmacokinetics of prednisone and prednisolone was studied. Two patients undergoing plasma exchange while receiving oral prednisone therapy were studied. Patient 1 received prednisone 50 mg daily; patient 2 received 60 mg daily. On a day when the patients were to undergo plasma exchange, blood samples for determination of prednisone and prednisolone concentrations were obtained just before the daily prednisone dose and at various times before, during, and after plasma exchange. The amount of both drugs in plasma removed by plasma exchange was also determined. On a day when the patients were not receiving plasma exchange therapy, additional blood samples were obtained just before the daily prednisone dose and at 0.5, 1, 2, 4, 6, and 8 hours after the dose. Values for elimination rate constant, half-life, area under the curve, clearance, and volume of distribution on and off plasma exchange were calculated from serum concentration-time curves for prednisone and prednisolone. Only prednisolone data proved adequate for pharmacokinetic calculations. Values of pharmacokinetic variables for prednisolone on and off plasma exchange did not differ substantially in either patient. The amount of combined prednisone and prednisolone removed by plasma exchange in each patient was less than 1% of the administered prednisone dose. In the two patients studied, changes in pharmacokinetic values for prednisolone attributable to plasma exchange and the amount of combined prednisone and prednisolone removed by plasma exchange were minimal. Supplemental dosing of prednisone following plasma exchange appears unnecessary.