Venocclusive disease (VOD) of the liver, a fibrous obliteration of small hepatic venules, can be caused by chemoradiation therapy. We reviewed 255 consecutive patients undergoing bone marrow transplantation for malignancy during 1978 to 1980 in order to determine the incidence of VOD and the predisposing factors. Fifty-three of 255 patients met our criteria for VOD, for an incidence of 21%. Multivariate analysis showed that the most significant risk factors for VOD were age over 15, an underlying malignancy other than acute lymphocytic leukemia and hepatitis prior to transplantation. Patients with hepatitis had a 3.4-fold risk of developing VOD, as compared to patients with normal SGOT values (p = 0.0004). Hepatitis in this setting is probably of non-A, non-B viral etiology and represents a relative contraindication to marrow transplantation because of enhanced toxicity from conditioning chemoradiotherapy.