Hepatitis C virus (HCV) infection is frequently found in autoimmune hepatitis and mixed cryoglobulinaemia. In these conditions HCV could be responsible for immuno-mediated organ alterations. The aim of this study was to evaluate the presence of immunological alterations in PCT patients, in which HCV infection has been frequently found. Twenty-three PCT patients were evaluated for clinical and serological alterations, including: chronic hepatitis, other systemic symptoms, serum cryoglobulins and rheumatoid factor (RF), haemolytic complement, serum immunoglobulins, anti-nuclear (ANA), anti-smooth muscle (ASMA), anti-liver-kidney-microsomal (anti-LKM1), anti-soluble-liver-antigen (SLA), anti-mitochondrial (AMA), anti-GOR antibodies, anti-HCV and HCV RNA. Abnormal serum ALT were present in the majority of cases (20/23, 87%), while liver biopsy revealed a chronic persistent hepatitis or chronic active hepatitis in 15/20 (75%) PCT patients. In a high percentage of subjects (91%) the presence of anti-HCV was detected by ELISA and RIBA II (Chiron, Emeryville CA, USA). In 17/22 (77%) cases the ongoing HCV replication in the serum was demonstrated by the detection of HCV genomes (polymerase chain reaction). The prevalence of both anti-HCV and HCV RNA in PCT was significantly higher if compared to 22 systemic immunological diseases (P < 0.001) and 47 healthy subjects (P < 0.001). A possible HCV-induced autoimmunity in PCT was suggested by the presence of the following immunological parameter alterations: anti-GOR in 13/23 (57%), ANA in 4/23 (17%), ASMA in 18/23 (78%), anti-LKM1 in 1/23 (4%), RF in 23/23 (100%), mixed cryoglobulins in 4/23 (17%), complement consumption in 10/23 (43%).(ABSTRACT TRUNCATED AT 250 WORDS)