This study analyzed factors associated with acute oropharyngeal herpes simplex virus (HSV) infection in 627 patients who had undergone allogeneic bone marrow transplantation for leukemia, lymphoma, or aplastic anemia. HSV infection developed in 233 (37%) of the patients; all but two were seropositive for HSV before transplant. Sixty-two percent of the seropositive patients had at least one episode of HSV reactivation during the first 100 days after transplant. Other factors that placed patients at increased risk for HSV infection were a pretransplant diagnosis of leukemia, being in remission at the time of transplant, and/or having been conditioned for transplant with chemoradiotherapy. Recognition of factors that may predispose patients to HSV infection helps determine those transplant recipients who might benefit most from antiviral prophylaxis or other approaches to prevention of HSV reactivation.