Hepatitis C virus-related chronic hepatitis may be associated with various immunological disorders. The aim of this study was to determine prospectively the prevalence of the clinical, biochemical and pathological immunological abnormalities in a series of 61 consecutive patients with chronic hepatitis C, compared with those in 61 age-and sex-matched control subjects without markers of hepatitis C virus and hepatitis B virus infections and with those in 61 patients with chronic hepatitis B. The following investigations were systematically performed before any treatment: detection of serum cryoglobulinemia and rheumatoid factor, detection of a large variety of serum antitissue antibodies, biopsy of labial salivary glands, ophthalmological examination, dosage of thyroid-stimulating hormone and in uiuo capillary microscopy. Cryoglobulinemia was found in 36% of the hepatitis C virus patients, four of whom had dermatological and/or neurological manifestations of vasculitis, and rheumatoid factor was present in 70%. Serum antitissue antibodies were detected in 41% of cases, mostly antinuclear and anti-smooth muscle antibodies. Liver-kidney microsomal and antithyroid antibodies were rare. Salivary gland lesions were found in 49% of the patients: all had lymphocytic capillaritis, sometimes associated with lymphocytic sialadenitis resembling that of Sjijgren's syndrome, but without features of sicca syndrome and Ro/SSA antibodies. Five percent of the patients had lichen planus. The prevalences of cryoglobulinemia, rheumatoid factor and antitissue antibodies were significantly higher than those in the control group and patients with chronic hepatitis B. In conclusion, hepatitis C virus-related chronic hepatitis may be associated with immunological abnormalities that can be classified into several categories: (a) immune complex-mediated disease, mainly represented by mixed cryoglobulinemia that, in rare cases, may be associated with symptoms of vasculitis; (b) au-