With increasingly widespread use of cyclosporine for the treatment of psoriasis, it is imperative to identify reliable markers of cyclosporine-induced nephrotoxicity. Five patients with extensive psoriasis and no significant preexisting renal disease were treated with oral cyclosporine (average dosage, 5 mg/kg per day; average duration of treatment, 9 weeks). Changes in serum creatinine measurements made immediately before and at the end of treatment were compared with changes in glomerular filtration rate as determined by 125I-iothalamate clearance. During treatment, the average serum creatinine value only increased from 1.0 +/- 0.2 to 1.1 +/- 0.3 mg/dl (+/- standard deviation), whereas iothalamate-based estimates of glomerular infiltration rate decreased from 100 +/- 22 to 63 +/- 37 ml/min/1.73 m2 (p less than 0.02). Simultaneous 125I-iothalamate and 24-hour creatinine clearances were obtained in two patients at the end of treatment and at 2 weeks after cyclosporine therapy. Glomerular filtration rates determined by iothalamate clearance were 14% to 30% lower than those calculated by 24-hour creatinine clearances. Neither serum creatinine measurements nor creatinine clearances (whether calculated or measured) accurately reflect the cyclosporine-induced decline in renal function as determined by glomerular filtration rate. In contrast, 125I-iothalamate clearance is a more accurate measurement of glomerular filtration rate, which provides a sensitive marker for monitoring potential cyclosporine-induced nephrotoxicity.