The intradermal route of hepatitis B vaccine administration has been tested in several clinical trials and has produced various degrees of immunogenicity, but usually among small groups of participants. To assess more adequately the immunogenicity of hepatitis B vaccine using the intradermal route, the Centers for Disease Control conducted a clinical trial among 425 well health-care workers in a hospital setting. Participants were randomly assigned to one of two treatment groups: those receiving a 20 micrograms intramuscular injection, and those receiving a 2 micrograms intradermal injection. Participants received the plasma-derived hepatitis B vaccine by the standard schedule at 0, 1 and 6 months, and serum samples were collected at 3, 8, 12 and 24 months after the first dose. Antibody response rates (anti-HBs titre greater than or equal to 10 sample ratio units by radioimmunoassay) for the intradermal vaccination group were consistently lower than those for the intramuscular vaccination group at each testing interval. The differences were greatest for the 3-month test and decreased over time. Geometric mean titres for anti-HBs for the intradermal group were significantly lower than those for the intramuscular group at the 8-month test point. In addition to inoculation route, factors of gender, smoking and age were found to have significant effects on immune response. The results suggest that intradermal vaccination with hepatitis B vaccine may be appropriate under certain conditions and for certain population subgroups.