The acceptance of the fetal allograft in the face of a completely competent maternal immune system remains a perplexing and critical problem in transplantation immunology . Varieties of potential mechanisms by which the fetus could avoid rejection have been proposed by Medawar (1) and by Billingham (2), and these proposals set the stage for much of the work in this field. The mechanisms proposed to prevent immune destruction of the fetus by the mother have postulated roles for blocking antibodies, immunosuppressive antibody-antigen complexes, nonimmunoglobulin immunosuppressive molecules, suppressor cells, and selective maternal immunoincompetence (reviewed in references 3-8). Many of these arguments turn on the question of what type of transplantation antigens encoded by the MHC are present in the placenta. Class I antigens have been demonstrated in the placenta of the mouse (9-13), human (14-21), and rat (22-24) using alloantisera and mAbs. Other studies in the human showed that the placenta also carries unique class I, or class I-like, antigens, the TLX antigens (25, 26), and class I molecules that carry only broadly crossreactive public antigenic determinants (27). Class II antigens are absent from the placenta in both the mouse (9, 28) and the human (14)(15)(16)(17)(18)(19) 29) .Studies in the rat demonstrated that during pregnancy the maternal strain in certain mating combinations made an antibody response to the paternal component of the fetal histocompatibility antigens without any prior sensitization (22, 30, 31) . The most potent response occurred when the u X a (female X male) haplotypes were mated. The alloantibody (22) and mAb (30) responses were directed against a placental class I molecule, the pregnancy-associated (Pa)' antigen, that has a broadly shared public antigenic determinant but not the allele-specific determinant of a classical class I transplantation antigen . The Pa antigen isolated from lymphocytes has a heavy chain of 46 kD and is associated with the ,B2-microglobulin molecule. It appears to be controlled by a diallelic system : the a, d, f, b, and m haplotypes carry the Pa antigen, whereas the n, c, l, u, g, k, and h haplotypes do not . Using alloantisera, both the Pa antigen and the allele-specific RT 1 .Aa antigen were shown to be in the basal, but not in the This work was supported by grants HD-08662 and HD-09980 from the National Institutes of Health.' Abbreviation used in this paper: Pa, pregnancy-associated.J. Exp. MED.