The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented. In 141 cases (37.5%) the syndrome was considered idiopathic. Among the secondary forms, chronic liver diseases and connective tissue diseases shared most frequently mixed cryoglobulins (18.8 and 15.4% of cases, respectively). Another common association was that with Waldenström's macroglobulinemia: cryoglobulins were found in 20% of these patients. In 5 patients (2 with the essential form and 3 with cryoglobulinemia secondary to Waldenström's disease) a Cl-inhibitor deficiency was discovered; the complement profile was characteristic of the acquired type and episodes of angioedema occurred. Studying the clinical course of 71 cases of essential mixed cryoglobulinemia followed-up for 4-20 years we concluded that the evolution of type II and type III cryoglobulinemias is different because that of type II seems to have a more severe course and may differentiate in a lymphoproliferative disorder; the immunochemical type of cryoglobulins seems therefore to have a prognostic significance. Because of the considerable overlap in the distribution of immunochemical types among the clinical subsets, a mixed classification (both biochemical and clinical) is proposed.