Female sexual contacts of men with nongonococcal urethritis (NGU) are often treated with either tetracycline or erythromycin because these antimicrobial agents are active in vitro against most strains of both Chlamydia trachomatis and Ureaplasma urealyticum, the major identified causes of NGU. Both drugs are known to be active against genital C. trachomatis infections in women. In this study, tetracycline and erythromycin base were evaluated for efficacy against U. urealyticum in the vagina. U. urealyticum was isolated from 400 (85%) of 473 women. Among women whose cultures for U. urealyticum were initially positive, cultures were negative at follow-up for one (1%) of 95 receiving no treatment, four (6%) of 71 receiving erythromycin base (250 mg four times daily for seven to ten days), and 59 (42%) of 142 receiving tetracycline (500 mg four times daily for five to ten days). Thus, none of the regimens is reliable for eradication of U. urealyticum from the vagina.