Ethane dimethanesulfonate (EDS), a compound cytotoxic to Leydig cells which causes transient infertility, was used in a 4 d post-exposure experimental protocol designed to identify any effects this compound might exert on the epididymis. The techniques of efferent duct ligation and testosterone(T) implantation were used to negate the role of testicular effects on the epididymal parameters. EDS was shown to affect the epididymis in a dose-dependent fashion. The action of EDS on the epididymis is in part due to the androgen deprivation caused by the elimination of Leydig cells in the testis since T implantation prevented some of the morphological changes in the epididymis, as well as some of the changes in sperm proteins and motility. However, neither efferent duct ligation nor T implanatation prevented the formation of sperm granulomas in the caput epididymis, the distinct morphological alterations of the corpus epididymis, the modification of certain sperm membrane proteins, or the decrease in the progressive motility and velocity of sperm following EDS treatment.