Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA-treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (f=.001), with no change in renal function over time (P=.6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttrans-plant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P=.001), sex (P=.001), cyclosporine toxicity (P=.024), and initial cyclosporine dosage (P=.016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection ep sodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PR A, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P=.001) and late rejection episodes (P=.001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity.