Breeding for fine black fur has generated a colony of mink wherein 20-30% of the males are infertile. Two clinical groups are distinguishable: one being infertile from the start (primary infertility), and the other infertile after one or more years of fertility (secondary fertility). Although the etiology of primary infertility is unknown, the available data indicate that secondary infertility is associated with an autoimmune disease of the testis. Thus, male mink with secondary infertility have (a) higher prevalence and levels of anti-sperm antibody when compared with animals with primary infertility, and the antibody prevalence varies with fur color; (b) severe monocytic orchitis (47%) and/or aspermatogenesis (75%) with negative cultures for bacterial, fungal, mumps, or Coxsackie B viral organisms; (c) massive and extensive granular deposits of mink IgG and/or C3 (71%), typical of immune complexes, along the basal lamina of seminiferous tubules; (d) testes that when eluted with buffer or low pH yielded IgG that was 10-fold enriched in anti-sperm antibody activity as compared with serum IgG; and (e) no immunopathologic evidence of Aleutian mink disease. Although the sperm antigen-antibody complexes in the testis may be important as a pathogenetic mechanism of the testicular disease, there is no correlation between fluorescent anti-sperm antibody detection in the serum and the infertile state. The infertile black mink is a new model of infertility associated with naturally occurring autoimmune disease of the testis.