Four patients with renal transplants developed hepatic veno-occlusive disease after immunosuppressive therapy with azathioprine. Severe progressive portal hypertension developed in all patients, with the clinical presentation varying from a mild viral-like syndrome to rapidly fulminant liver failure and death. The disease was associated with cytomegalovirus infection but not with the dose of azathioprine, the type or duration of transplant, or the type of underlying kidney disease. In view of the high mortality rate associated with veno-occlusive disease (a combined 55% in our four patients and in five reported in the literature) and wide spectrum of clinical presentation in patients with renal transplants, a high index of suspicion is required and aggressive intervention indicated.