Mouse embryos at the two-cell and blastocyst stages, as well as unfertilized eggs, have been studied by indirect immunofluorescence for the expression of H-2 and non-H-2 histocompatibility antigens on surface membranes. Serologically-specific reactivity to non-H-2 antibody (H-3 and H-6) was observed as diffuse, patchy staining over the entire surface of the blastomeres at the two-cell stage. In contrast, no reactivity of two-cell or unfertilized egg embryos of four inbred strains was observed when antisera containing only multispecific H-2 cytolytic antibody were used. Antisera containing H-2 along with non-H-2 antibody of unknown specificity showed varying degrees of reactivity, which could be shown by absorption studies to be due to the non-H-2 content of the serum. The results suggest that the initial expression of histocompatibility genes varies and support the hypothesis that the appearance of these cell components may relate to specific stages of differentiation.