A number of cell populations in the reproductive tract show a response to vasectomy. Some cell types show similar responses in man and all laboratory species, whereas others show marked species variations. This chapter describes these effects in a broadly chronological order and, in a general way, considers changes close to the site of vasectomy first and the longer term effects on the testis itself later. Following vasectomy, epididymal distension and sperm granuloma formation result from raised intraluminal pressure. The sperm granuloma is a dynamic structure and a site of much spermatozoal phagocytosis by its macrophage population. In many species, spermatozoa in the obstructed ducts are destroyed by intraluminal macrophages, and degradation products, rather than whole sperm, are absorbed by the epididymal epithelium. Humoral immunity against spermatozoal antigens following vasectomy is well established and there is evidence of modest T-lymphocyte activity. The role of lymphocytes in the reproductive tract epithelium and interstitium following vasectomy is poorly defined. In laboratory animals, there is evidence that pressure-mediated damage to the seminiferous epithelium can follow sperm granuloma formation and obstruction in the epididymal head. However, the contribution of lymphocytes and antisperm antibodies to testicular damage after vasectomy is far from clear. A number of studies have suggested that testicular changes may follow vasectomy in man but their validity and mechanism of occurrence require further study.