Six of 325 patients undergoing renal transplantation under combined cyclosporine (CsA)-prednisone immunosuppression displayed renal artery thrombosis between 4 and 12 days after transplantation. All six patients had satisfactory initial revascularization, as ascertained by radionuclide scan and renal function. In none was the thrombosis considered to be secondary to rejection, either by clinical course or upon renal biopsy. Since there was no clear etiologic factor and since none of the overlapping 297 patients treated with azathioprine-prednisone displayed this complication, these cases appear to support the hypothesis that CsA alters intravascular hemostatic homeostasis. Data in experimental models are consistent with a predisposing factor to thrombosis, namely CsA reduces the synthesis of prostacyclin stimulating factors, leading to decreased prostacyclin production by vascular endothelial cells, and to failure to inhibit platelet aggregation.