Guinea pigs with experimental allergic orchitis show an acute inflammation in the rete testis and epididymis. At these sites anti-sperm antibody is bound to sperm. The role of antibody in the production of disease was investigated. It was found that guinea pigs immunized to sperm antigens in complete Freund's adjuvant have autoantibodies in serum which bind in in vitro tests to the surface membrane of immature and mature sperm cells. The anti-sperm antibody when injected into normal guinea pigs, either systemically or in the interstitium of the testis, binds to sperm inside the rete testis and produces a mild acute inflammatory reaction at that site. Also, ¹²⁵I-labeled IgG from normal guinea pigs when injected into the testis can cross the wall of the rete testis into the lumen. Anti-sperm antibody and normal Ig, on the other hand, do not appear to penetrate the seminiferous tubules. The main barrier for the crossing of Ig into the seminiferous tubules may be the layer of cells external to the basement membrane. Thus, antibodies to basement membrane injected locally do not bind to the tubular basement membranes. Hence, the results suggest that antibody, although not directly involved in the production of aspermatogenesis, can produce an acute inflammatory reaction by binding to the sperm in the sperm passage system.