PIP: Because stilbestrol (DES)-associated vaginal adenosis appears shortly after onset of puberty, this study was undertaken to assess the effectiveness of local treatment with progesterone as an inhibitor of ovarian estrogens, the possible etiological agents of vaginal adenosis. 5 teen-age women were studied; the mother of each had received varying amounts of DES during the patient's time in utero. The biopsy-proven adenosis cases were marked by redness, squamous pegs, and chronic inflammation before treatment with 20-mg progesterone suppositories, inserted vaginally, 2 times/day. (9 figures depict the cytological appearance of the subjects' vaginas before and after therapy.) Regression of the adenosis occurred in all 5 subjects; regression was marked clinically by gradual elimination of redness of the vaginal mucosa as well as reduction of inflammation, as observed microscopically. In 3 of the 5 patients, no evidence of vaginal adenosis was found on biopsy post-therapy. In the other 2 patients, residual adenosis was confined to the cervical area. Serum progesterone concentrations were measured throughout the study by radioimmunoassay and were found to be low in the 1st half of the cycle (.75-2.3 ng/ml), but the levels increased to high luteal-phase values by the 2nd half of the cycle (8.7-24.5 ng/ml). No alterations in menstrual patterns were seen. Local progesterone application may have great value in treatment of vaginal adenosis, particularly that associated with DES exposure in utero. Therapy with progesterone resulted in regression of disease without interfering with ovulatory patterns.