The presence of H-2 and non-H-2 alloantigens on the 3 1/2-day mouse blastocyst was investigated with use of the technique of ectopic transplantation to preimmunized recipients. Macroscopic and histological examination of graft sites 1–10 days after transfer revealed that blastocysts of donor strains differing from the hosts either at combined H-2 and non-H-2 loci, or at non-H-2 loci alone, were inhibited in their development, while those from donors differing only at the H-2 locus developed normally, irrespective of the presence or absence of the zona pellucida at the time of transfer. F1 hybrid blastocysts between strains differing only at non-H-2 loci were significantly inhibited whichever parent contributed the paternal component. The histological evidence showed that transplanted blastocysts continued development for 2–3 days before exhibiting extensive host cell infiltration leading to embryo death. Following zona removal, the host response occurred after only 24 hr, indicating that antigens are present on the blastocyst at the time of transfer.