This paper reviews earlier studies identifying 3 possible immunologic causes of infertility: autoimmunity, ABO blood group incompatibility, and isoagglutination, and presents results of recent studies, including an analysis of the incidence of isoagglutinations, autoagglutinations, and ABO incompatibility in a group of couples with unexplained primary or secondary infertility and couples with an organic cause of infertility; incidence of antibodies in postpartum women, women in early pregnancy, unmarried women, and prostitutes; the relationship between ABO incompatibility and/or sperm-agglutinating antibodies to postcoital testing of cervical mucus; results of condom therapy in couples with positive isoagglutinins; a comparison of hemagglutination test with the microagglutination test; and preliminary studies of the immunoglobulin responsible for a positive microagglutination reaction. Results obtained from 292 women and 176 men indicated that in the 64 couples with primary unexplained infertility, 24 wives had isoagglutinins and 5 of the husbands had autoagglutinins. Among 32 couples with secondary unexplained infertility, 16 wives had isoagglutinins and only 1 husband had autogglutinins. 50 couples with organic causes of infertility and 25 unmarried women had a 20% incidence of isoagglutinins. Positive serologic reactions were found in 35 of 48 prostitutes. 15 of 44 women in the 1st trimester of pregnancy had isoagglutinins to at least 1 of 3-5 donor semen specimens, but serums of 7 of the women gave negative reactions when tested against the husband's ejaculate. The 2 women in the group who aborted had negative antibody titers. Only 1 of 29 serums from postpartum women gave positive agglutination reaction. Among 68 couples, 19 subjects had positive microagglutination test reactions but only 7 had positive hemagglutination reactions. No specific relationship was found between ABO incompatibility and the results of postcoital testing of cervical mucus in 58 women tested or positive circulating issoagglutinins in 62 women tested. 27 of 68 couples with primary unexplained infertility, 18 of 33 with secondary unexplained infertility, and 13 of 46 with organic causes of infertility had ABO incompatiblity. Autoagglutination, unless massive, was not incompatible with pregnancy. Circulating antisperm antibodies fell to undetectable levels after 2-12 months of condom therapy. Careful timing of ovulation is essential because of the increase in antibodies after reexposure. Results of condom therapy in terms of pregnancies were disappointing.