The clinical and immunochemical classification of 166 patients with cryoglobulinemia are presented. 52% of the cryoglobulins were detected in patients hospitalized because of various causes. The most frequent association was with liver and lymphoproliferative diseases (in particular with Waldenström's macroglobulinemia); two thirds of the patients with liver diseases presented with a purpura-arthralgia syndrome, and the hepatic involvement was only brought to evidence by subsequent laboratory investigation. The presence of cryoglobulins did not usually interfere with the clinical course of the basic condition. In 79 patients the cryoglobulinemia was considered idiopathic. In order to study the natural course of the disease in the idiopathic cases, a group of 35 patients had been followed up for 8-17 years: 37% developed a membranous proliferative glomerulonephritis, and more than half died of renal insufficiency; in 11% cirrhosis was diagnosed after a period of 4-9 years; another 11% developed a lymphoproliferative disease; of the remaining 40%, 2 are still asymptomatic, and the others are affected by purpura-arthralgia syndrome.