Cross reactivity in the HL-A system has been evaluated quantitatively by utilizing human cultured lymphoid cells and soluble HL-A antigens in cross absorption and cross inhibition assays. Most of the cross reactions among different HL-A specificities determined with platelets or peripheral lymphocytes were confirmed in this study. Some cultured lymphoid cells or soluble HL-A antigens possessing a cross reacting specificity cross absorbed a certain anti-HL-A antiserum, whereas others with the same specificity did not. The number of cells required to absorb cytotoxic HL-A alloantisera directed against cross reacting specificities is significantly greater than that necessary to absorb alloantisera directed against HL-A determinants present on the cell surface. This observation suggests that relatively small numbers of available antigenic determinants react with the cross reacting antibodies. The differential absorbing capacity of different cultured cell lines for the same cross reacting HL-A alloantibodies suggests a variability in the cell surface expression of cross reacting HL-A determinants.