BACKGROUND: Considering the immunosuppression of patients with chronic liver disease, their response to vaccination is discussed in literature. AIMS: To evaluate the response of hepatitis B vaccine in patients with chronic hepatitis C virus infection. METHODS: This is a prospective study in which 85 patients with chronic hepatitis C virus infection (46.8 +/- 9.4 years, 44.7% males) and 46 healthy adults (36.7 +/- 11.1 years; 39.1% males) were evaluated. Confirmation of hepatitis C virus was obtained by the technique of polymerase chain reaction. Viral load was determined by the branched DNA method in 74 patients, and genotype was determined by sequencing in 73 patients. All patients and healthy adults received three doses of Engerix B vaccine IM (at 0, 30 and 180 days). Serological responses to the vaccine were divided into three categories: seroprotection, when anti-HBs was > or =100 mUI/mL; seroconversion, when anti-HBs was 10-99 mUI/mL, and non-reagent, when anti-HBs was <10 mUI/mL. RESULTS: The response of hepatitis B vaccine as determined 1 month following dose 3 was seroprotection in 37.7%, seroconversion in 17.6% and non-reagent in 44.7% among patients and 84.8%, 13.0%, 2.2%, respectively in healthy adults. The number of non-reagent responses was significantly higher among those patients with chronic liver disease. Sixty-five patients with chronic hepatitis were compared to 20 compensated cirrhotic patients in concern to the response to vaccine, but no difference was found. The response to vaccine in patients with genotypes 2 or 3 (n = 40) was better than in those with genotype 1 (n = 33). Response was not related to serum HCV-RNA concentration. CONCLUSION: The number of non-responders was higher in patients with chronic hepatitis C virus infection, irrespective of histological status and viral load. It is suggested that such patients should receive a double dose of vaccine, particularly the ones with genotype 1.