Nasal immunization was studied to determine if it could elicit an immune response capable of preventing vaginal colonization by Neisseria gonorrhoeae or of reducing its duration in the estradiol-treated mouse model. Nasal administration of gonococcal outer membrane (OM) preparations induced the development of systemic and vaginal immune responses that were directed mainly against a limited number of gonococcal OM proteins. The impact of nasal immunization on vaginal colonization by N. gonorrhoeae was evaluated by use of an experimental model, in which mice were treated with estradiol to prolong the infection. Bacterial clearance was significantly faster for mice immunized intranasally with N. gonorrhoeae OM preparations (4.0+/-2.5 days) than for control mice (8.5+/-4.3 days). The estradiol-treated mouse model may serve as a useful tool for the evaluation of potential gonococcal vaccine candidates.