Antilymphocyte xenoantisera were produced in rats and rabbits against A/J (referred to as A) mice and in sheep against B6AF1 mice. Cytotoxicity tests with sera showed that cross reacting antigens of mouse and rat were detected by rabbit and sheep antisera and that cross reacting antigens of mouse, rat, and rabbit were detected by the sheep antiserum. Cross inhibition of cytotoxicity of this antisera by the corresponding Fab' or F(ab')2 fragments showed that sheep anti-A Fab' fragments inhibited the cytotoxicity of antisera produced in all species of animals tested; rabbit anti -A F(ab')2 fragments inhibited the cytotoxicity of anti-A sera produced in rabbit, rat, and in C57BL/6J and C3H mice, but not that of the sheep antiserum; rat anti-A F(ab')2 fragments inhibited the cytotoxicity of rat, C57BL/6J, and C3H anti-A sera, but not that of rabbit and sheep. Some of the H-2 antigens of A cells were recognized by the xenogeneic species as demonstrated by the residual cytotoxic activity of anti-A sera after absorption with cells of different strains of mice. It was deduced that alloantigenic determinants and species-specific antigenic determinants reside in close proximity on the cell surface or may be even on the same molecule, and that the range of cell surface antigens recognized by a xenoantiserum varies with the species which produced the antiserum.