To investigate the relationships among cytomegalovirus infection, sexual behavior, human immunodeficiency virus (HIV) seropositivity, and indexes of cellular immunity, 180 homosexual men and 26 heterosexual men were studied. Among the homosexual men, cytomegalovirus seropositivity was associated with increased T8 lymphocyte counts (p less than 0.001) and reduced T4/T8 ratios (p = 0.006); these results were independent of HIV infection. Cytomegalovirus seropositivity was also associated with increasing age, numbers of sexual partners, and the practice of anal-receptive intercourse. At the first visit, cytomegalovirus was isolated from none of 13 cytomegalovirus-seropositive heterosexual subjects, compared with 62 (36 percent) of 171 seropositive homosexual men (p less than 0.005). Viral isolation was most common from semen. Among 32 cytomegalovirus-seropositive homosexual subjects from whom culture specimens were obtained more than four times over 10 to 30 months, 72 percent of the specimens were culture-positive. The mean duration of cytomegalovirus excretion in semen was 22 months, and in urine, the duration was nine months. Cytomegalovirus excretion was associated with younger age and reduced lymphocyte proliferation in response to cytomegalovirus, but not with antibody to HIV. Cytomegalovirus infection is sexually transmitted among homosexual men, perhaps by rectal intercourse, and is associated with alterations in T lymphocyte subsets. Most seropositive homosexual men excrete cytomegalovirus intermittently, primarily in the semen.