To test the hypothesis that cytomegalovirus (CMV) is sexually transmitted, we examined the association of CMV infection with indices of sexual activity in 347 women attending a sexually transmitted disease (STD) clinic. Stepwise multivariate logistic regression analysis showed that seropositivity to CMV (complement-fixation antibody titer, greater than or equal to 1:8) was most closely associated with number of sex partners in the subjects' lifetime (P less than .0001), young age at first sexual intercourse (P = .0002), and nonwhite race (P = .0007). Among seropositive women, cervical shedding of CMV was most strongly associated with younger age (P = .0001) and the presence of cervical chlamydial infection (P = .016). Among 84 seronegative women followed up for a mean of 18.4 weeks, 11 (13%) developed primary CMV infections, an annual incidence of 37%. Sexual contact seems to be an important mode of acquisition of CMV in some young women.