Aggregate analyses of the impact of long-term cyclosporine administration in kidney transplant recipients have reported generally impaired but stable allograft function. In contrast, experience in extrarenal transplantation has suggested that treatment with cyclosporine for periods in excess of 12 months causes a progressive native nephropathy often leading to dialysis dependence. The extent of this apparent discrepancy between native kidneys and renal allografts is the subject of this study, which examines the evolution of renal function in 119 kidney and 100 heart transplant recipients receiving 12 or more months of cyclosporine immunosuppressive therapy administered in uniform protocols by affiliated clinical transplantation programs. The evolution of renal function in both study cohorts was analyzed retrospectively on the basis of serial serum creatinine (Crs) determinations. Assessment of group mean Crs, reciprocal Crs (1/Crs), and slopes of the curves obtained by plotting 1/Crs versus time in individual patients revealed a significant decline of native kidney function over the first 6 posttransplant months in the cardiac allograft group. Thereafter, however, native kidney function stabilized in these patients, and the aggregate trend was suggestive of no further decline in function over a 3- to 4-year follow-up period. Kidney transplant recipients had an aggregate trend of slowly declining allograft function consistent with the effects of chronic immunologic injury. The data were not consistent with a uniform pattern of a progressive, cyclosporine-induced loss of renal function in either cohort. Long-term use of cyclosporine was found to be associated with impaired but generally stable aggregate renal function in both the heart and the kidney transplant cohorts.(ABSTRACT TRUNCATED AT 250 WORDS)