Female Swiss Webster mice were immunized intraperitoneally with mouse epididymal spermatozoa or with phosphate buffered saline (PBS) and their fertility was compared by (1) incidence and size of litters, (2) number of uterine implantation sites, and (3) incidence and number of fertilized eggs in the oviducts. Statistically significant reduction in fertility was noted following two courses of injections of spermatozoa; 12% of mice injected with spermatozoa had litters compared with 80% of mice injected with PBS. The infertility did not seem to be related to a failure in fertilization since the two groups of mice had a similar incidence and number of fertilized eggs in the oviducts. All female mice were found to have a "natural' anti-acrosomal antibody. Following immunization with spermatozoa, antibodies to "postacrosomal' region, the main piece and the midpiece of the tail, as well as cytotoxic antisperm antibodies, appeared. Anti-LDH-X antibody was not detected. However, correlation was not found between infertility and antisperm antibodies or sperm granulomata that developed in the peritoneal cavities. It is concluded that female mice receiving repeated i.p, injections of mouse spermatozoa become infertile and that the infertility is related to interference with events after fertilization.