Neisseria gonorrhoeae were cultured from the urethra of male patients and from the cervix and urethra of female contacts. Isolates from a given group of individuals were of the same strain but differed considerably in terms of the molecular weight of both protein II and pili. Radioimmunoprecipitation assays showed that most patients produced serum antibodies to protein I. Antibodies to pili, when present, showed limited cross-reactivity with the different pili produced by a single strain. Antibodies to protein II were highly specific, reacting with only one of the protein II-types produced by a single strain; this observation suggested that the host immune response may be an important factor in antigenic variation. Several sera also contained antibodies to a common surface protein with a molecular weight of 43,000 that was present in all strains tested.