The immunologic relation between mother and fetus has become of interest to those concerned with reproductive physiology. One method to assay this type of relation is to determine the immunologic response to HLA antigens expressed by the fetus which are of paternal origin. Although 20 to 50% of multiparous women develop lymphocytotoxic antibodies during pregnancy, the effect of these antibodies on gestation or the fetus has not been established. In a prospective study, 23 patients at the time of spontaneous abortion had negative cytotoxic antibodies. Of 129 obstetric patients followed with antibody screening over a 6 to 7 month period until delivery, 28 developed positive lymphocytotoxic antibodies (22%). These 28 patients with cytotoxic antibodies delivered male infants by a ratio of 4 to 3, and 11 patients (39.3%) had complications during the gestation. The responsiveness to the paternal histocompatibility antigens is valuable information for furthering the understanding of the fetal-maternal relation.