The effects of prevalent and incident cytomegalovirus (CMV) infection on human immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera (median date, November 1983). CMV-seropositive subjects were one and a half times more likely to develop AIDS, and they were also older than CMV-negative subjects. Adjusted for age, CMV seropositivity was not associated with the development of AIDS. In age-adjusted analyses, CMV-seropositive subjects had a small, but statistically insignificant, decrease in survival after HIV seroconversion. Older subjects were more likely to CMV seroconvert by the time of their latest available serum samples (P = .03). CMV seroconverters were five times more likely to develop clinical CMV disease than were subjects initially CMV-positive (P = .02). To avoid this source of serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be exposed to cellular blood products or body fluids from CMV-seropositive donors.