To determine antibody responses to small doses of human diploid cell rabies vaccine (HDCV), we determined rabies antibody titers in 124 volunteers who had been vaccinated with one of five primary preexposure regimens. In a sixth group of 47 persons previously vaccinated with duck embryo rabies vaccine (DEV), we evaluated the booster responses after a 0.1-mL dose of intradermal (ID) HDCV. Persons in all five groups undergoing primary immunization received three doses of vaccine, one each on days 0, 7, and 28. The dose and route of vaccination for the five groups included 1 mL intramuscular (IM), 0.1 mL ID (two subgroups), 0.1 mL subcutaneous (SC), and 0.25 mL SC. Adequate titers developed in all persons, irrespective of the route or quantity of vaccine. The geometric mean titers (IU/mL) on day 49 in those receiving primary regimens were 12.87 (1.0 mL IM), 7.44 (0.1 mL ID by syringe), 3.05 (0.1 mL by jet injector), 3.17 (0.1 mL SC), and 6.47 (0.25 mL SC). Titers on day 90, while lower, were still acceptable. Adequate antibody titers developed in all persons previously vaccinated with DEV after a single 0.1-mL ID dose of HDCV; however, higher titers developed at day 7 in those who had shown an adequate response to DEV in the past. Results of this study suggest that HDCV may be used ID or SC for primary preexposure rabies prophylaxis and ID for booster immunization.