Serum IL-6 levels have been shown to correlate with disease severity and prognosis in patients with plasma cell dyscrasias. Among its pleiotropic actions, IL-6 is also the major regulator of the acute phase response in humans. The possible impact on survival of the major serum acute phase proteins (s.APP) [C-reactive protein (s.CRP), alpha-1-antitrypsin (s.AAT), haptoglobin, acid alpha-1-glycoprotein and alpha-2-macroglobulin (used as control)] was assessed on a population of 103 consecutive, previously untreated myeloma patients. Univariate analysis showed that among the acute phase proteins only s.AAT (P = 0.015) and s.CRP (P = 0.027) were significantly correlated with survival. The multivariate Cox proportional hazard model applied to s.APP and other common parameters showed that s.beta-2-microglobulin (s.b2M), s.calcium, s.creatinine, BM plasma cell percentage, age and s.AAT correlated significantly with survival. Combining s.b2M and s.AAT allowed stratification of myeloma patients: those with low levels of s.b2M (< or = 3 mg/l) and of s.AAT (< or = 3 g/l) presented an excellent prognosis (median survival exceeding 10 years) while those presenting higher values of the two parameters presented a median survival of 2.5 years (P = 0.002).