Human autoantibody to Sertoli cells was detected in normal human sera. This IgM type autoantibody was undetectable during the neonatal period and was found in 11.5% of 365 serum samples taken from adult healthy persons of both sexes. This human autoantibody to Sertoli cells exhibited quite the same target‐organ specificity and multi organ reactivity (salivary gland ductules, pancreatic intercalated duct, renal lower nephron, pituitary acidophilic cells) as those of the murine monoclonal autoantibody (IgM class) to Sertoli cells (TM‐1: WHO registered code T43). The TM‐1 monoclonal antibody could recognize testicular antigens with molecular weights of 67,000 and 23,000 in Sertoli cells, and had already been demonstrated capable of inducing murine experimental spermatogenic disturbance when administrated together with murine monoclonal autoantibody to seminiferous tubular basement membrane (TNI 2: WHO registered code T44). These observations may suggest that human spermatogenic disturbance could be easily induced by the multi‐organ reactive autoantibody to Sertoli cells even in healthy individuals under particular conditions where this autoantibody can be allowed to reach the target Sertoli cells across the barrier of seminiferous tubular wall by either autoantibody to seminiferous tubular basement membrane or other toxic damage. Acta Pathol Jpn 41: 879‐888, 1991.