To assess the prevalence and risk factors for cryoglobulinaemia associated with hepatitis C virus (HCV) infection, we studied 360 consecutive patients with chronic hepatitis C (191 men, median age 57 years; 86 [24%] with cirrhosis). One-hundred and sixty-eight (47%) had circulating cryoglobulins (mean levels 208 +/- 256 mg l-1), predominantly of type III (80%; and 20% type II). Cryoglobulins were more common in women than in men (56% vs 39%, P=0.001) and in patients with cirrhosis than in those with chronic hepatitis (57% vs 43%, P=0.024). Cryoglobulinaemic patients more frequently had high levels of serum immunoglobulin M (IgM) (57% vs 30%, P=0.001), immunoglobulin G (IgG) (84% vs 70%, P=0.002) and rheumatoid factor (45% vs 16%, P=0.001); low levels of serum C3 (15% vs 4%, P=0.001) and C4 (51% vs 26%, P=0.001); and low numbers of platelets (21% vs 12%, P=0.018), than patients without cryoglobulins. The presence of cryoglobulins was not correlated with hepatitis duration (cryopositives, 12 +/- 7 years; cryonegatives, 11 +/- 8 years) or HCV genotype (HCV 1b, 48% vs 53%; HCV 2a, 35% vs 29%, cryopositive vs cryonegative patients respectively). By multivariate analysis, female gender (odds ratio [OR] 1.675; confidence interval [CI] 1. 055-2.661), elevated serum IgM (OR 2.296; CI 1.438-3.665), IgG (OR 1. 952; CI 1.114-3.422), rheumatoid factor (OR 3.213; CI 1.889-5.465) and low C4 (OR 1.859; CI 1.138-3.038) could reliably predict the presence of cryoglobulins. When the pathogenic variables IgG, rheumatoid factor and C4 were excluded from analyses, only levels of serum cholinesterase activity < 4500 U independently predicted (OR 3. 663, CI 1.258-10.184) the presence of cryoglobulins. Fifty per cent of the patients with chronic hepatitis C circulated cryoglobulins, with preference for those with a greater impairment of liver function, as revealed by serum cholinesterase activity.