Plasma fibronectin (FN) was measured in 17 patients with essential mixed cryoglobulinaemia (EMC) and in 17 normal subjects by single radial immunodiffusion (RID) and enzyme-linked immunosorbent assay (ELISA). In 9 patients the presence of FN in the cryoprecipitates was also assessed by immunoblotting. In the EMC group, plasma FN levels were significantly lower than in control subjects, using both methods, and FN was constantly demonstrated in EMC cryoprecipitates. Capillaroscopic observation of the capillary bed in skin and bulbar conjunctiva, performed in all cases, showed severe alterations of microcirculation in EMC patients. A negative correlation between plasma FN and capillaroscopic abnormalities of skin capillaries was observed. These data support the hypothesis that plasma fibronectin plays a role in the pathogenesis of systemic vasculitis in EMC.