Summary. The cross‐reactions of M and N antibodies and the MN antigens of human tissue cells in culture have been investigated by mixed agglutination. Cross‐reactions have been found chiefly between the N antigen of tissue cells and anti‐M and anti‐N antibodies; and between anti‐N antibodies and the M antigen of red cells.Attempts were made to reduce cross‐reactivity by testing the cells at different temperatures and after treatment with enzymes. These conditions were also imposed upon red cells in direct agglutination using the same antisera but there was little correlation between the results of the direct agglutination and mixed agglutination tests.