Veno-occlusive disease (VOD) can develop in association with the administration of cytotoxic chemotherapeutic agents and irradiation. In solid-organ transplant settings, azathioprine has been implicated as a predisposing factor. VOD with fatal outcome occurred in a postliver-transplant recipient who had never been exposed to any agents that have the potential to induce VOD. At onset, the disease manifested clinically as gross ascites and progressive jaundice and was observed after clinically diagnosed acute graft rejection. The disease was confirmed by histologic examinations. Histologic studies of biopsy samples from this patient revealed that most small hepatic veins less than 300 &mgr;m in diameter were affected, exhibiting concentric intimal thickening with sparse inflammatory cells. A few of the hepatic veins exhibited active endotheliitis with occasional extension of inflammation to neighboring centrilobular areas. Despite intensified immunosuppression, the observed fibrous obliterative changes were irreversible. Although the cause of VOD in this patient is tentative, the damage to the endothelium, associated with acute rejection, is likely to be attributable. VOD deserves recognition as one of the causes for liver dysfunction and persistent ascites after liver transplantation.