Maternal antipaternal immunity was compared between a group of 12 couples with normal reproductive histories and a group of 13 couples with obstetrical histories of more than one consecutive stillbirth or repeated pregnancy loss subsequent to having had successfully carried to term. Couples were studied for maternal-paternal HLA antigen sharing and for maternal antihusband immunity in tests detecting both complement dependent and independent antibodies as well as in an assay measuring direct cell-mediated cytotoxicity. There was no significant difference in the proportion of HLA antigen sharing between these two groups; however, the women in the pregnancy loss group demonstrated significantly more antipaternal immunity than their normal childbearing counterparts and more than previously described for aborting couples who share HLA antigens. Screening of the cytotoxic sera on a well characterized cell panel failed to reveal alloreactivity patterns consistent with paternal HLA antigen profiles. These data demonstrate that certain women who suffer recurrent pregnancy losses can mount vigorous immune responses to paternal lymphocyte antigens. We propose that the appearance of such lymphocytotoxins represents inappropriate maternal immune responses to fetal extraembryonic antigens that may subsequently result in fetal demise.