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The relationship between exogenous contraceptive hormones and  permissiveness of the female genital  tract  to human immunodeficiency virus type 1 (HIV-1) is the subject of renewed debate.  To better characterize the effect of depot  medroxyprogesterone acetate  (DMPA) on HIV-1 cellular  targets  and  epithelial integrity in the vagina, we  compared leukocyte  populations, markers of activation and  proliferation, and  the  density of intercellular junctional  proteins in the vaginal  epithelium of women during the follicular  and  luteal  phases  of the menstrual cycle and  approximately 12 weeks  after receiving  a DMPA injection. This prospective cohort  study involved 15 healthy  women. Vaginal  biopsies  were  obtained in the follicular  and  luteal  phases  of the menstrual cycle, and approximately 12 weeks  following  a 150-mg intramuscular injection  of DMPA. Leukocyte  populations, activa- tion phenotype, and  epithelial tight  junction  and  adherens proteins were  evaluated by immunohistochemistry. After receiving DMPA, the numbers of CD45, CD3, CD8, CD68, HLA-DR, and CCR5 bearing  immune cells were significantly ( p < 0.05) increased in vaginal  tissues,  compared to the follicular  and/or luteal phases  of untreated cycles. There were no significant  differences  in immune cell populations between the follicular and luteal phases of the control  cycle. There were  also no statistically significant  differences  in epithelial thickness  and  density  of epithelial tight junction  and  adherens proteins among  the follicular, luteal, and  post-DMPA treatment sampling points.  In this  pilot  study,  vaginal  immune cell populations were  significantly altered  by exogenous proges- terone,  resulting in increased numbers of T cells, macrophages, and  HLA-DR- and  CCR5-positive cells.