Among 78 patients with persistent cold agglutinins, 31 had lymphoma, 13 had macroglobulinemia of Waldenstrom, six had chronic lymphocytic leukemia and 28 had chronic cold agglutinin disease. The average age was over 60 years. Patients wit chronic cold agglutinin disease had more hemolytic crises, bleeding and Raynaud's phenomena, and less frequently lymphadenopathy or hepatosplenomegaly. The frequency of anemia, positive Coombs test results, cryoglobulinemia and Bence Jones proteinuria was similar in the various groups. Survival time from diagnosis was on average two years in lymphoma, two and a half years in Waldenstrom's macroglobulinemia, more than six years in chronic lymphocytic leukemia and more than five years in chronic cold agglutinin disease. Anti-I were common in chronic cold agglutinin disease (74 percent) and rare in other groups (32 to 33 percent). Anti-I and other cold agglutinins were rare in chronic cold agglutinin disease and common in lymphoma and Waldenstrom's macroglobulinemia. In chronic cold agglutinin disease, and in Waldenstrom's macroglobulinemia, cold agglutinins usually had K light chains--92 percent and 71 percent, respectively--whereas in lymphoma, 71 percent of cold agglutinins had lambda light chains. The type of light chains related to the specifically of cold agglutinins: 58 percent of IgM/K were anti-I, 75 percent of IgM/lambda had other specificities. Cold agglutinins were cytotoxic to autologous and allogeneic cells were killed implying that the former may be precoated in vivo with the antibodies. In conclusion, conditions with persistent cold agglutinins are a spectrum that varies from "benign" autoimmune-like chronic cold agglutinin disease to malignant lymphoma. Marked differences in the light chain type of cold agglutinins, specificity toward membranous antigens and severity of clinical manifestations were noted in benign and malignant varieties.