To determine whether cytomegalovirus (CMV) infection in teenage girls is related to sexual activity, 254 girls 12-18 years old (mean, 15.8) attending a contraceptive counseling clinic were studied. Participants were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, and serum antibody to CMV was determined. Demographic and sexual history data were collected by interview. The mean number of lifetime sex partners was 2.2; 173 (68%) were seropositive. Race, greater than 3 years of sexual activity, and greater than 2 lifetime sex partners were significant risk factors for CMV infection (odds ratios [OR], 1.8-4.7; P less than .05). Using logistic regression analysis, a composite sexual activity variable was the most important risk factor for CMV infection (OR, 4.8; P = .003), followed by race (OR, 3.4; P = .004) and a sexually transmitted disease composite variable (OR, 2.4; P = .016). Sexual activity is an important risk factor for CMV infection in adolescent girls.