Because HIV and hepatitis B virus share many common risk factors, it is important to try to vaccinate HIV patients against hepatitis B. There are numerous reports describing a variety of dose schedules, limited success and markers associated with impaired response to HBV vaccine in these individuals. All studies have been small in size making it difficult to draw conclusions within and between studies. The purpose of this study was to evaluate a double dose of hepatitis B vaccine under more definitive guidelines: double blinded, randomized, controlled, with numbers for statistical validity. Two hundred and ten HIV infected subjects received a standard dose (20 microg) or a double dose (40 microg) of recombinant hepatitis B vaccine IM 0, 1 and 6 months. Ninety-four receiving standard dose and 98 receiving double dose completed the study. The seroconversion rate (anti-HBs > or = 10 mIU/mL) was 47 and 34% for double dose and standard dose, respectively (p = 0.07). A statistically significant higher seroconversion rate was associated with double dose comparing with standard dose for patients with CD4 cell counts > or = 350 cells/mm3 (64.3% x 39.3%; p = 0.008) but made no difference to seroconversion in those with CD4 <350 (23.8% x 26.3%; p = 0.80). Double dose also improved seroconversion comparing with standard dose for patients with HIV viral load <10,000 copies/mL (58.3% x 37.3%; p = 0.01) but made no difference to seroconversion in those with HIV viral load > or = 10,000 copies/mL (16% x 17%; p = 0.7). Based on the results of this study, the best current strategy for hepatitis B vaccination in HIV patients would be to use a double dose as a primary series when the viral load is likely to be low and CD4> or = 350, when there is likely to be an adequate immune response.