The ultrastructural pathology of the initial segment of the rat caput epididymidis was examined after oral administration of a single high dose of the antifertility compound α-chlorhydrin (U-5897) at time intervals ranging from two hours to nine days after treatment. At doses in excess of 30 mg/kg this compound produces a lesion specifically localized in the initial segment of the epididymis characterized by sloughing of the epithelium, which leads to obstruction of the lumen of the epididymal duct, spermatocoel and sperm granuloma formation and an ultimate occlusive fibrosis. In rats fed 140 mg/kg of U-5897 the first effects can be seen as early as two hours after treatment. Within 48 hours after treatment, the lumen of the greater part of the initial segment is filled with degenerating cells and debris which block further passage of sperm along the duct. The present study provides insight into the nature of the early events in the evolution of this epididymal lesion. Possible mechanisms of action of α-chlorhydrin are discussed.