Hepatitis C virus infection is a major cause of nonA, nonB hepatitis worldwide. A high prevalence of immunological abnormalities has been shown to occur in patients with chronic hepatitis C virus infection.The aim of this study was to assess the development of sicca syndrome in a cohort of patients infected with a single strain of hepatitis C virus, namely genotype 1b, and correlate this with viral persistence and human leukocyte antigen type of the patients.Ninety-five patients infected with the single strain hepatitis C virus were used in this study, 32 of whom were polymerase chain reaction-negative and 63 polymerase chain reaction-positive. Patient details were reviewed for symptoms consistent with sicca syndrome. Human leukocyte antigen class I (A, B and C) and class II (DRB and DQB1) typing was performed on all patients. Auto-antibodies were also measured.DQB1*02 was highly significantly associated with viral persistence (P<0.0001). Nineteen of 21 patients with sicca syndrome were hepatitis C virus-polymerase chain reaction-positive demonstrating a strong association with viral persistence and the development of the syndrome. Human leukocyte antigen DQB1*02 was significantly associated with the development of sicca syndrome, P=0.02.The development of autoimmune disease in patients with chronic hepatitis C virus infection depends on the interaction of multiple factors. This study suggests that important factors in this process are viral persistence and human leukocyte antigen type of the patients.