To analyze possible causative mechanisms for intracranial hemorrhage after orthotopic liver transplantation. We conducted a retrospective survey of medical records and a case-control comparison in patients who had undergone liver transplantation during the period 1986 through 1992. In a group of 8 patients with intracranial hemorrhage after orthotopic liver transplantation and a control series of 207 patients who had undergone liver transplantation but did not have intracranial hemorrhage, we summarized pertinent clinical and laboratory data and statistically analyzed potential risk factors for hemorrhage. In the eight study patients, intracerebral hematomas were located in the parietal or frontal lobe in six, the cerebellum in one, and the putamen in one. Autopsy demonstrated a Candida-associated mycotic aneurysm in one of the eight patients, and one had disseminated aspergillosis. No statistically significant differences in thrombocytopenia, hypertension, extracranial bleeding sites, or cyclosporine-related neurotoxicity were found when these patients were compared with the control series. Bacteremia or fungemia was found in five of the eight patients with intracerebral hemorrhages (62%) but in only 11 % of the control group (P = 0.03; Fisher's exact test). Overwhelming infections, thrombocytopenia, or both may have a role in intracerebral hemorrhage after liver transplantation.