Urogenital infections in postmenopausal women remain problematic. The use of estrogen replacement therapy has been shown to lower these infection rates, corresponding to increasing colonization by Lactobacillus species. Despite the gut's 500 microbial species and the proximity of the anus to the vagina, only a relatively few microbial strains appear to be able to colonize the urogenital area. In the present study, the sparsity of microbes in the vagina was confirmed by denaturing gradient gel electrophoresis analysis of swabs taken at time zero and monthly for 3 months from 40 postmenopausal subjects receiving Premarin (conjugated equine estrogen in combination with progesterone) hormone replacement therapy (HRT) and 20 who were not on HRT. Lactobacilli were recovered from the vagina of 95% or more women in both groups, but in the HRT group, Lactobacillus were more often the dominant and only colonizers and significantly fewer bacteria with pathogenic potential were found. The incidence of bacterial vaginosis was significantly lower in the HRT group than in the non-HRT-treated women (5.6% versus 31%). The use of HRTs has recently come under criticism. The ability of drugs such as Premarin to help recover the lactobacilli vaginal microbiota appears to be at least one benefit of HRT use. In women not using HRTs, use of probiotics may be the only way to restore a nonpathogen-dominated flora.