The purpose of this work was to evaluate in a case-control study the immunogenicity of a recombinant hepatitis B virus (HBV) vaccine in patients with chronic hepatitis C. Seventy-seven patients with histologically proven chronic hepatitis C without cirrhosis were included in a prospective trial and matched for sex and age to 231 healthy adult subjects. Recombinant HBV vaccine was administered at a dose of 20 microg at months 0, 1 and 2. The definition of 'responder to vaccination' was anti-HBs titre > 10 mIU/ml after the three injections. Forty-nine (63.6%) chronic hepatitis C patients were responders to vaccination, compared with 217 (93.9%) controls (P < 0.0001). After the three injections, anti-HBs titres were 156 +/- 260 and 615 +/- 435 mIU/ml (P < 0.0001), respectively. Chronic hepatitis C patients who were non-responders to vaccination had significantly higher viral load than responders to vaccination. Moreover, a negative correlation was observed between viral load and anti-HBs concentration (r = -0.36, P = 0.003). No significant side effects were observed. There was no effect of vaccination on alanine aminotransferase (ALT) levels and hepatitis C virus (HCV) viral load during or after vaccination. In multivariate analysis, the main predictive factors of response to HBV vaccine were absence of anti-HCV antibodies (OR = 7.65, P < 0.0001), weight < 75 kg (OR = 1.99, P < 0.035), and age < 50 years (OR = 1.58, P < 0.082). Our results suggest that viral load seems to negatively influence the response to HBV vaccine.