In order to elucidate the way in which the epididymis and vas deferens first react to and dispose of the continuous influx of spermatozoa from the testis after vasectomy, the effects of vas obstruction have been studied in the rabbit, rhesus monkey, hamster, and rat. Initially, spermatozoa accumulated in and began to distend the vas deferens and the distal portion of the epididymis, but the response thereafter varied from species to species and sometimes among individuals within a species. The distensibility of the distal segment of the rabbit tract seemed to ensure its integrity for 24 weeks or more, but focal ruptures of the duct wall (granulomata) appeared in one or more regions of the epididymis by 32 weeks in most rabbits. In the monkey, discrete granulomata developed along the vas deferens and/or in the cauda epididymidis only 5-6 weeks after vasectomy in some individuals, and this coincided with the subsidence of a small but palpable enlargement of the cauda epididymidis. Macroscopic granulomata erupted in one or more regions of the hamster epididymis within 8 weeks and some 30 percent of these animals displayed a terminal cyst at the point of vasal obstruction. In the rat, the consistent early development of a similar eruption at this site seems to alleviate sperm build-up proximal to the obstruction and, as a probable consequence, epididymal granulomata appeared less frequently in this species.