OBJECTIVE To test the hypothesis tha a very-low-dose regimen of vaginal estrogen would provide effective relief from atrophic vaginitis without endometrial proliferation. METHODS Twenty postmenopausal women with symptoms, signs, and cytologic evidence of atrophic vaginitis were enrolled. Each subject was treated with 0.3 mg of conjugated estrogens, administered vaginally 3 nights per week for 6 months. We examined the following outcomes: symptoms, vaginal cellular (cytologic) maturity, endometrial histology, sonographic evaluation of endometrial thickness, Doppler measures of uterine artery blood flow, and serum levels of estrone and estradiol. Pre- and post-treatment data were compared for each subject. RESULTS Satisfactory relief of symptoms occurred in 19 of 20 cases. Vaginal cellular maturation improved significantly with therapy (P < .01). There were no significant changes in endometrial thickness, uterine artery blood flow, or serum estrogen levels. Endometrial proliferation was observed in one case. CONCLUSIONS Relief from atrophic vaginitis can be achieved with 0.3 mg of conjugated estrogens administered vaginally three times per week. Endometrial proliferation may occur at this low dose, albeit rarely.