Twenty-eight patients undergoing marrow transplantation participated in a pilot study to determine the safety of continuous infusion heparin for the prevention of veno-occlusive disease (VOD) of the liver. Four doses of continuous infusion heparin were administered, ranging from a dose prolonging the partial thromboplastin time (PTT) to 1.5-2.0 times the patients' baseline value, to a dose prolonging the PTT to less than 1.2 times the patients' baseline value. Seven patients (25%) received a full course of heparin, beginning from the day the preparative therapy started through day 14 post-transplant (range 20-26 days on heparin). In 21 patients infusions were ended before day 14 post-transplant, a median of 16 days on heparin (range 1-26 days). Of these, 14 patients were withdrawn from heparin because of bleeding and seven were withdrawn because of anticipated bleeding. Bleeding was observed in 27 patients and was minor in 25. Two patients developed major bleeding in the gastrointestinal tract which was not fatal. Minor bleeding was observed in 27 of 28 case control patients who did not receive heparin. The sites of bleeding were similar in control and heparin treated patients. VOD developed in 20 patients (71%) and was sever or fatal in four (14%). The prevalence of VOD was not influenced by the dosage of heparin or the duration of its administration. We conclude that low dose heparin resulting in marginal prolongation of the PTT may be infused into patients undergoing marrow transplantation with a low risk of serious bleeding. Further studies are needed to evaluate its efficacy.