OBJECTIVES: The efficacy of the standard hepatitis B virus (HBV) vaccination schedule in individuals with chronic hepatitis C is reported to be reduced. Our aim was to assess the response rate to high dose, short interval HBV vaccination in such individuals. METHODS: A total of 152 individuals with chronic hepatitis C were vaccinated with 40 microg of vaccine administered monthly for 3 months. Twenty-six individuals with no evidence of liver disease underwent the same vaccination schedule and were considered to be the control group. Hepatitis C virus (HCV)-positive subjects who did not seroconvert to anti-hepatitis B surface positivity after the third dose of the vaccine (nonresponder) were vaccinated with a fourth dose of vaccine (booster dose, 80 microg). RESULTS: One hundred nine of the 152 individuals with chronic hepatitis C (72%) seroconverted to anti-hepatitis B surface positivity (> 10 mIU/ml), as compared to 24 of the 26 controls (92%, p < 0.05). Although individuals with chronic hepatitis C responded less frequently to high dose, short interval HBV vaccination than did the controls, no differences in terms of effective immunity (>100 mIU/ml) were evident among the two groups of responders (51% vs 54%). Also, no difference in response was reported between individuals with chronic active hepatitis C and controls (92% vs 80%). The response rate was significantly lower in cirrhotics than in the noncirrhotic group (54% vs 80%, p < 0.001). Besides cirrhosis, no other demographic or bioclinical factor was found to influence the response to vaccination. After the additional booster dose, the overall response was increased to 74% of the cirrhotics and 88% of the noncirrhotics. No major HBV vaccine-related adverse effects were seen. CONCLUSIONS: A high dose, short interval HBV vaccination schedule is safe in individuals with chronic hepatitis C. From these data, it is suggested that a high dose and a short interval between HBV vaccinations may produce an effective and early antibody response in such patients.