About 40 years ago Bordet demonstrated that agglutinins did not ordinarily agglutinate bacilli unless salt was present, and until recently it has been customary for all immunologists to regard the process of specific agglutination as involving two separate stages; first, a primary, specific, and rapid combination of antibody with antigen, and second, a slower stage-requiring the presence of an electrolyte-during which the primary compound particles aggregated. Bordet (1920) believed that the second stage was not serologically specific. He spoke of it as belonging to the "domaine de la physico-chimie." Marrack (1934) in a stimulating monograph on antigens and antibodies proposed a speculative explanation of antibody-antigen reactions involving a purely chemical mechanism throughout. He supposed that each molecule of the antibody had a number of specific combining groups, and through the medium of these groups the molecules or particles of the antigen, which we know to contain numerous specifically reactive groups, were thus tied together. Later, Heidelberger and Kendall (1935) proposed a similar mechanism for the precipitin reaction. This hypothesis has been called the "alternation" theory.It soon became evident that these two theories of agglutination predicted rather different results from the mixing of two independent serological systems. That is, if two different antigens and their respective antibodies were to be mixed, according to the Bordet theory the second stage of agglutination, being nonspecific, should take place irrespective of the type of antigen: sensitized antigen '"X" could combine with sensitized antigen "Y," and mixed clumps, or "agglutinates," should be obtained. According to the newer theory of Marrack and of Heidelberger and Kendall, however, this should not occur, because the linkage is supposed to be serologically specific at all stages. The first attempt to test this was made by Topley, Wilson, and Duncan (1935). They mixed two kinds of bacteria, pneumococci and enteric bacilli, with their respective antisera and observed that the resulting aggregates were homogeneous, that is, each clump was composed either of pneumococci or of bacilli but not of the two simultaneously. This result was in agreement with the predictions of the newer theory of agglutination. Later, however, Abramson (1935) mixed human erythrocytes and Friedliander bacilli with their respective antibodies and found that heterogeneous clumps were obtained. A possible objection to this experiment was the radically different nature and size of the two antigenic particles-bacteria and erythrocytes-15 on July 31, 2020 by guest http://jb.asm.org/ Downloaded from on July 31, 2020 by guest