To clarify the rise in plasma creatinine concentration previously observed during prednisone treatment, we studied changes in renal function in Graves' ophthalmopathy patients before and after 2 weeks of either prednisone 60 mg/day or retrobulbar radiotherapy (controls). Compared to retrobulbar radiotherapy, prednisone treatment was associated with an increase in: (a) plasma creatinine concentration (from 68 +/- 4 to 76 +/- 4 mumol/l), (b) glomerular filtration rate (GFR, from 93 +/- 4 to 102 +/- 5 ml/min/1.73 m2), and (c) urinary creatinine excretion rate (from 510 +/- 40 to 570 +/- 40 mumol/h). We conclude that GFR rises during 2 weeks of high-dose prednisone administration, a rise that is not reflected by a decrease in plasma creatine concentration. On the contrary, both plasma creatinine concentration and urinary creatinine excretion increase, probably as a result of the catabolic effect of prednisone. As established by the present study, prednisone 60 mg/day is associated with protein wasting, also after 14 days of treatment.