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The epidemiology of mucosal candidal colonization and candidiasis was studied in a multicenter cohort of 871 human immunodeficiency virus (HIV)-seropositive and 439 demographically and behaviorally similar HIV-seronegative women. Cross-sectional analyses at baseline revealed that oropharyngeal colonization withCandidaspecies was more prevalent among seropositive women and among women reporting recent cigarette smoking and injection drug use. Oropharyngeal candidiasis was also more prevalent among seropositive women. Both oropharyngeal colonization and candidiasis were significantly associated with a lower median CD4 lymphocyte count among seropositive women. Vaginal candidal colonization was more prevalent among seropositive women and among those reporting recent injection drug use and current insulin or oral antihyperglycemic therapy. Vaginal candidiasis was equally likely to be diagnosed in seropositive and seronegative women and was not significantly related to recent sexual contact. Neither vaginal colonization nor candidiasis was significantly related to a lower median CD4 lymphocyte count among seropositive women. Baseline evaluation indicated differences in the epidemiology of oropharyngeal and vaginal candidal colonization and candidiasis in HIV-seropositive women and suggested possible variation in pathogenesis of candidal infection at these two mucosal sites.