Experimental infection of the vagina of TO and CBA mice with Mycoplasma pulmonis was enchanced greatly by progesterone treatment. Almost all treated animals became infected, whereas only two-thirds of the untreated TO mice and less than half of the untreated CBA mice did so. Almost 1000-fold more organisms were recovered from treated than from untreated mice and the duration of infection was more than doubled. The enhanced infection in the hormone-treated animals was accompanied by a more severe vaginal polymorphonuclear leucocyte response which reached a maximum two weeks after inoculation of M. pulmonis. In the TO mice the eventual decline in cellular response coincided with the gradual disappearance of the mycoplasmal infection. The implications of these findings for genital infections of other animal species are discussed.