IL-6 is now recognized as a growth factor for plasma cells as well as a C Reactive Proteine inducer. This prompted a reappraisal of acute phase reactants in monoclonal gammapathies. Eight acute phase proteins were assayed in patients with multiple myeloma (n = 51), MGUS (n = 17) and Waldenström's macroglobulinemia (n = 5). The CRP level was above 10 mg/l in 27% of all myeloma patients, in 39% of patients with active myeloma, in 4 of 5 patients with Waldenström's macroglobulinemia and in none of the MGUS patients. Fibrinogen, alpha-1-antitrypsin and orosomucoid levels were significantly higher in the myeloma group than in the MGUS group. Differences were not significant for haptoglobin, ceruleoplasmin, transferrin, and alpha-2-macroglobulin. Serial assays in 22 myeloma patients showed that CRP levels were correlated with disease activity. A biologic inflammatory syndrome, defined as a significant variation in two or more acute phase reactants, was demonstrated in 41% of myeloma patients, 18% of MGUS patients, and 60% of Waldenström's macroglobulinemia patients. Active disease was significantly more common among myeloma patients with biologic evidence of inflammation, as compared with myeloma patients without biologic inflammation. These data suggest that similarly to IL-6 acute phase reactants are markers for disease activity in multiple myeloma.