A large proportion of the sera from 574 parous women was shown to contain cytotoxic antibodies against HL-A tissue antigens. After their second pregnancies, one-quarter of the women had cytotoxins, and after the sixth, one-half of the women had these antibodies. Retrospective studies of the outcome of pregnancies showed that women with antibodies had a significantly higher incidence of infants with congenital anomalies than did those without antibodies. It is postulated that antibodies produced by the mother against incompatible HL-A antigens of the fetus may have a deleterious effect upon the fetus in subsequent pregnancies.