We administered up to 6 monthly doses of hepatitis B vaccine to 16 chronic carriers of hepatitis B surface antigen (HBsAg) in an attempt to eliminate the antigen. The HBsAg in this vaccine differs from native antigen. No patient had elimination of HBsAg, but one of 10 no longer carried hepatitis B e antigen (HBeAg). Of 13 patients without preexisting antibody to HBsAg (anti-HBs), none acquired the antibody; two of three patients with preexisting heterotypic anti-HBs had transient, low-level increases in anti-HBs titers. Serum alanine aminotransaminase (ALT) levels fell in eight patients, remained unchanged in six, and increased transiently in two. Decreased ALT and HBeAg clearance, however, did not seem to be related to vaccination, and the transient ALT elevations appeared to represent sporadic, acute non-A, non-B hepatitis. No adverse effects other than sore arm and joint pain were seen. Immunization of chronic HBsAg carriers with hepatitis B vaccine, although ineffective in eliminating HBsAg, appeared to be safe. Such safety, if confirmed, would simplify the design of hepatitis B vaccination programs.