In past studies Mycoplasma hominis has persisted after treatment with placebo, penicillins, or rifampin in 88-97% of women and 49-77% of men with infections of the lower genital tract. Among women with nonspecific vaginitis, M. hominis persisted in only a third of those treated with metronidazole as compared with at least 70% of those treated with ampicillin (P = 0.01), even though M. hominis is resistant in vitro to metronidazole and to its acid and hydroxy metabolites. Persistence of M. hominis after treatment with metronidazole was significantly associated with persistence of Bacteroides species in the vagina (P = .03). These results suggest that colonization of the vagina with M. hominis is partly dependent on other components of the vaginal microbial flora. In prior studies, M. hominis has persisted in zero to 50% of women and in zero to 30% of men after treatment with tetracycline or lincomycin, but the role of tetracycline resistance in treatment failure was not defined. The susceptibility of M. hominis to tetracycline is bimodal; and the minimal inhibitory concentration (MIC) of tetracycline for strains isolated before or soon after treatment was greater than or equal to 16 micrograms/ml for seven (78%) of nine that did persist and for two (17%) of 12 that did not persist after tetracycline therapy for cervicitis in women (P = .002). The MIC of tetracycline was greater than or equal to 16 micrograms/ml for two (12%) of 17 isolates from women in Seattle in 1972-1973, as compared with 27 (34%) of 79 isolates from Seattle men and women in 1979-1982.(ABSTRACT TRUNCATED AT 250 WORDS)