Acquired cystic kidney disease (ACKD) is a common complication in patients treated with long-term dialysis. Previous studies performed prior to the cyclosporin A (CsA) era indicate that successful renal transplantation causes regression of ACKD. Little has been published, however, on the occurrence of ACKD in CsA-treated transplant recipients. We conducted a prospective sonographic study in 33 renal transplant recipients and 32 dialysis patients to evaluate the effect of CsA on ACKD in transplant recipients. Transplant recipients had a lower prevalence (39% vs. 56% in dialysis patients) and severity (smaller kidneys and lower cyst grades) of ACKD when compared with dialysis patients. Renal cell carcinoma was found in two dialysis patients. Using multiple regression analysis, we found that the use of CsA was significantly correlated with the presence of ACKD in transplant recipients (57% in CsA-treated vs. 8% in non-CsA-treated patients). We conclude that renal transplantation reduces the prevalence and severity of ACKD in the native kidneys; however, among transplant patients, CsA administration is associated with a greater prevalence of ACKD.