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This study was done to define antigens important in the immune response to infection with Neisseria gonorrhoeae. Sera were obtained from men and women with uncomplicated gonorrhea (DOC), women with disseminated gonococcal infection, and women with gonococcal pelvic inflammatory disease (PID); sera were also obtained from uninfected controls. Vaginal fluids were taken from 15 patients with UCO or PID. The sera and vaginal fluids were tested against gonococcal isolates from the same patients to examine homologous antibody-antigen interactions by use of the western blot technique. Antibodies in the serum reacted with more gonococcal antigens compared with antibodies in the vaginal fluid. IgO in serum and vaginal fluid reacted with more antigens than did IgA in the same specimens. The predominant antigens reactive with IgG in serum were pili, protein II, a broad 23–33-kDa band of antigen, and presumptive lipopolysaccharide; and for IgA, protein II and a 46–48-k-Da protein. The control sera also reacted with the 46–48-kDa protein. The predominant antigens reactive with IgO in vaginal fluid were protein I, protein II, pili, and the 46–48-kDa protein; and for IgA, protein I, protein II, and pili. Immunoglobulin in vaginal fluid reacted comparatively more with protein I than did immunoglobulin in serum. [ABSTRACT FROM PUBLISHER]