In an investigation of the possible role of IgA1 protease in the initial encounter of Neisseria gonorrhoeae with human genital mucosa, the pathogenicity of an isogenic, piliated, wild-type gonococcal clone was compared with that of its IgA1 protease-deficient mutant in organ cultures of human fallopian tubes. The fallopian tube mucosa released IgA into the organ culture medium throughout the course of the infection; the rate of release was substantially higher in gonococcus-infected organ cultures. The wild-type gonococcus but not the IgA1 protease-deficient mutant elaborated IgA1 protease into the medium. The rate and extent of attachment, damage, and invasion of the fallopian tube mucosa by the IgA1 protease-deficient mutant were indistinguishable from those by the parental clone. These data are compatible with the hypothesis that, in the initial encounter with previously uninfected human genital mucosa, the production of IgA1 protease is not critical to the ability of the gonococcus to act as a mucosal pathogen.