RABBIT antibodies of the immunoglobulin G (IgG) class have been shown to be cleaved by pepsin, in the absence of mercaptans, into bivalent fragments¹. These fragments, termed F(abâ ²)²-fragments, sediment in the ultracentrifuge at 5S and are resistant to further cleavage. Similar products have been observed after peptic digestion of human IgG antibodies². In contrast, others found that human immunoglobulin M (IgM) was rapidly degraded by pepsin into a heterogeneous mixture of small fragments^{3â 5}. Incubation of IgM cold agglutinins with the enzyme in buffer at pH. 4.0 and 37° C for 30 min, or 4° C for 48 h, resulted in the complete loss of red cell agglutinating activity³. Efforts to demonstrate residual combining activity by an indirect agglutination technique were unsuccessful. Similarly, treatment of IgM anti-γ-globulins (rheumatoid factors) by pepsin at 4° C for 48 h resulted essentially in complete loss of activity, as measured by several agglutination methods³. I have examined further the degradation of human IgM anti-γ-globulins by pepsin and present evidence of the production of fragments that retain the capacity to combine with human IgG.