Eight cases of hepatitis due to herpes simplex virus (HSV) (five “confirmed,” three “possible”) were identified among marrow-transplant recipients at the Fred Hutchinson Cancer Research Center between 1975 and 1988. The clinical and pathological characteristics of these patients are described and compared with published findings for non-marrow-transplant recipients with HSV hepatitis. Clinical syndromes in the marrow-transplant recipients ranged from fever associated with abdominal pain and elevations in serum aminotransferase levels to fulminant hepatitis. Evidence of hepatic infection appeared before day 20 following transplantation unless prophylaxis with acyclovir was given, in which case HSV hepatitis did not appear until after day 40. All patients died, although the one patient who was given early, empirical high-dose acyclovir therapy clearly improved with antiviral therapy and may have died of other causes. Involvement of multiple organs with HSV was found in three of four patients with confirmed HSV hepatitis who underwent autopsy. In all cases, reactivation of latent HSV was the presumed source of the HSV hepatitis. HSV hepatitis should be considered when HSV-seropositive recipients of marrow transplants develop abdominal pain, fever, and elevations in aminotransferase levels.