The use of cyclosporine therapy for heart transplant recipients has been associated with a significant improvement of graft survival. Renal function impairment is a frequent finding in patients chronically treated with cyclosporine. The purpose of this prospective randomized study was to establish renal function in a group of heart transplant recipients receiving chronic cyclosporine treatment and to test the hypothesis of reversibility of cyclosporine-induced nephropathy by late reduction of cyclosporine. A total of 28 patients who underwent operation at least 18 months before this study began were randomly assigned to either group A (n = 14), in which the whole-blood polyclonal cyclosporine target trough level was reduced from 400 to 600 micrograms/L to 200 to 400 micrograms/L, and group B (n = 14), in which the level was maintained at 400 to 600 micrograms/L. Renal and cardiac function were assessed by paraaminohippuric acid, inulin and lithium clearances and heart catheterization, respectively, at entry and 4 months later. Cellular rejection in the transplanted heart was monitored by at least four endomyocardial biopsies every 14 days with the histologic Texas scale (grading: 0 to 10). In heart recipients renal blood flow (592 +/- 202 ml/min/1.73 m2) and glomerular-filtration rate (74 +/- 33 ml/min/1.73 m2) were significantly lower (p < 0.01), and mean arterial blood pressure (109 +/- 13 mm Hg) and renal vascular resistance (22.4 +/- 9 mm Hg/dl/min/1.73 m2) were significantly higher than the corresponding values in normal controls (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)