Liver disease in the early period following bone marrow transplantation may be due to a number of causes, including pretransplant cytoreduction with chemotherapy and irradiation. Although the relationship of venoocclusive disease to these agents has been well established, another process, nodular regenerative hyperplasia, may also occur. In this retrospective study, we evaluated the incidence and clinical signs of these two processes as defined by histological criteria. In 103 patients studied, nine (8.8%) had venoocclusive disease and 23 (22.5%) had nodular regenerative hyperplasia. Venoocclusive disease was significantly associated with transplantation for malignancy other than acute or chronic leukemia and use of busulfan as a cytoreductive agent and occurred in younger patients. Nodular regenerative hyperplasia did not differ from the general transplant population in terms of underlying disease, cytoreductive regimen, graft vs. host disease prophylaxis or age. Both venoocclusive disease and nodular regenerative hyperplasia were associated with ascites. Venoocclusive disease had a poor prognosis, with eight of nine cases dying of or with venoocclusive disease, whereas no case of nodular regenerative hyperplasia died of liver disease and only 5 of 23 died with nodular regenerative hyperplasia. Using retrospective data, five of 11 patients fulfilling clinical criteria for the diagnosis of venoocclusive disease actually had nodular regenerative hyperplasia, as did all of nine patients fulfilling the criteria for "possible" venoocclusive disease. These results indicate that nodular regenerative hyperplasia is a process which occurs commonly following bone marrow transplantation and which may be clinically misdiagnosed as venoocclusive disease.