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KANOH, T. The Behavior of Immunoglobulin in Monoclonal Gammopathies and Their Classification and Pathogenesis. Tohoku J. exp. Med., 1970, 102 (4), 369 401•\Quantitative measurements of immunoglobulins were made in sera from 203 patients with monoclonal gammopathies. In IgG myeloma the serum IgG concentration averaged six times the normal level, in IgA myeloma 15 times, and in IgD myeloma 370 times the normal values of respective proteins. In primary macroglobulinemia the average serum level of IgM was 38 times higher than normal. The serum levels of the normal immunoglobulin classes were markedly decreased in these diseases, including Bence-Jones myeloma and biclonal myeloma. Various mechanisms were proposed to account for the reduction of normal immunoglobulins. On the other hand, in benign monoclonal gammopathy there was usually no reduction of normal immunoglobulins. However, in patients with cancer and IgG or IgA-M-components IgM levels were decreased. The reason for lowered IgM value remains obscure. It was of special interest that one of the patients with a potentially malignant type appeared to be developing myeloma. A marked reduction of the normal immunoglobulin classes seems to be a poor prognostic sign in patients with M-components in the absence of myeloma. Since patients with lymphoma have a marked tendency to hypogammaglobulinemia and closely resemble a primary-malignant group, immunoglobulin changes in patients with lymphomas and M-components are more complicated. A classification of monoclonal gammopathies was proposed on the basis of their pathogenesis after the consideration of our data as well as those from the literature. The concept of the pathogenesis of monoclonal gammopathies presented herein is based on the view that lymphomas, immunologic deficiency diseases, and autoimmune diseases form a 'trinity' pathogenetically and etiologically.•\monoclonal immunoglbulins; monoclonal gammopathy; plasma cell myeloma