The humoral response of rats to mouse xenografts included production of antibodies that detected the major histocompatibility alloantigens of donor mice with remarkable specificity. Although these antibodies were present in high titer, their effects were generally masked by “species-specific” activity until after appropriate absorptions. The absorption process produced significant anticomplementary activity in the absorbed sera, which may explain difficulties previously experienced in recognizing allospecificity in xenoantisera. The fact that histocompatibility alloantigens, unlike other alloantigens, are recognized readily by a xenogeneic host may indicate greater homology between major histocompatibility antigens of different species than was previously recognized.