Intradermal immunization of mice against hepatitis B surface antigen (HBsAg) using a novel real-time controlled jet injector was assessed by comparison with intradermal and subcutaneous injection of antigen using a 27G needle and syringe. Three doses of aluminium-absorbed HBsAg were delivered at 0, 14, and 28 days. Antibodies to HBsAg were detected only in mice injected with antigen with antibody levels increasing with secondary injections. Mice vaccinated by intradermal injection using the jet injector or subcutaneous needle injection exhibited comparable immune responses at day 47. Differences in titer observed between intradermal jet injected and needle injected animals reflect differences in the volume of antigen delivered. With the exception of minor bleeding at the injection site in a few animals injected either by jet injection or needle, no adverse events were observed in any of the mice used in the study.