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Protein catabolic rate (PCR) was measured daily by computerized mass balance studies in 50 subjects during hospitalization after renal transplant. All subjects received 60 mg prednisone per day. PCR rose over the first 3 to 4 postoperative days and then stabilized at an accelerated level, which was sustained through the third posttransplant week. Rejection therapy with either 3 mg/kg/d prednisone or 15 mg/kg/d of methylprednisolone for 3 days further increased PCR, but there was no difference in PCR between these two regimens. Protein restriction did not decrease PCR and subjects offered a higher protein diet did not have further acceleration of PCR. We conclude that 60 mg/kg/d prednisone produces an obligatory acceleration of PCR that is further accentuated by higher steroid doses. The use of minimal maintenance doses of prednisone consistent with adequate immunosuppression seems wise. Protein balance may be improved if protein intake is increased to match individual rates of accelerated protein catabolism.