Immunological deposits in the testis and circulating antibodies to spermatozoa are presented as a possible explanation for infertility in man. Testicular biopsy specimens from infertile patients (N= 52) as well as from fertile controls (N= 6) were analyzed immunohistochemically by using semithin sections. Immunoglobulin deposits were found in the testes of 21 patients. Antibody deposits were observed on the seminiferous tubule wall, on germ cells or in the interstitium. In two cases, the C3 complement component was detected on the tubular wall and in one case on atypical spermatogonia. Deposits of immunoglobulin class G were found most frequently, and were often attached to the seminiferous tubule wall. In addition, the occurrence of circulating antisperm antibodies in the sera of these patients was examined by a recently developed method, the immunobeads binding test. A significant number of patients with normal spermatogenesis had antibodies that exhibited a strong binding reaction to spermatozoa as observed by the immunobeads binding test. It is suggested that at least two different immunological mechanisms may be involved in pathological infertility: an immunoglobulin deposit, induced locally in the testis, in a manner specifically against the germ cells and the seminiferous tubular basement membrane, or in a manner nonspecifically against seminiferous tubular wall, and asystemically induced immunoglobulin production which is directed against spermatozoal antigens.