ABSTRACT: Sera from three fertile men and four infertile men without sperm antibodies, 17 infertile men with sperm antibodies in serum and seminal plasma (S.P.), and 25 infertile men with sperm antibodies in S.P. were tested by Western Blot analysis against sperm membrane extracts and S.P. from fertile nonautoimmune men and infertile autoimmune men. Sera from fertile men reacted against common antigens with molecular weights (MW) of 28, 38, 48, 60, and 68 kD present on sperm from autoimmune and nonautoimmune men and special antigen of MW 76 kD on the sperm of fertile men. Sera from 15 of 17 (88%) autoimmune infertile men with sperm antibodies in serum and S.P. detected special antigens with MW of 58 kD (sera reactivity in 47% of these men), 43kD (in 29%), 30 kD (in 24%), 35 kD (in 18%), 52 kD (in 12%), 41 kD (in 6%), and 71 kD (in 6%) on the sperm of autoimmune men in addition to the common antigens. Sera from 15 of 25 (60%) men with sperm antibodies in their S.P. showed reactivity to special antigens with MW 52 kD (in 20%), 35 kD (in 16%), 41 kD (in 16%), 58 kD (in 8%), 70/71 kD (in 8%), 30 kD (in 8%), and 56 kD (in 4%). Sera from 18 of 42 (43%) infertile men with sperm antibodies also detected special antigens of MW 26, 46, and 76 kD present only in fertile men's sperm. Sera from only 15 of 42 (36%) autoimmune infertile men reacted against special antigens with MW 17, 20, 23, 30, 43, and 58 kD in the seminal plasma of autoimmune infertile men. Cross-absorption studies using sera from autoimmune infertile men further supported the presence of unique antigens on their sperm. It is proposed that the special antigens present on the sperm from infertile autoimmune men may be responsible for the enhanced humoral and cell-mediated immune responses observed in these men.