BACKGROUND Postexposure treatment (PET) of travelers who may have had a potential rabies exposure is simpler, safer, and cheaper if the traveler is preimmunized. Preimmunization can be done with human diploid cell rabies vaccine (HDCV) administered intramuscularly or intradermally. Some authorities, however, are now advocating that travelers vaccinated by the intradermal (ID) route should be treated as if they are not immunized. A particular concern raised is that travelers who have received pre-exposure rabies vaccination intradermally, may have a delayed response to postexposure boosters. This study is designed to elucidate whether a single intramuscular (IM) HDCV booster will provoke an early (day 5) immune response in individuals given pre-exposure ID HDCV. METHODS Twenty-nine travelers who had received a course of three 0.1 mL ID HDCV between 12 and 24 months previously were given a single 1.0 mL IM booster of HDCV. Rabies antibody levels were compared 5 days later to those before the booster. RESULTS Twenty-five of the 29 subjects (86%) showed an adequate rise in virus neutralizing antibody (VNA) titer 5 days after booster. Nine of the 29 subjects (31%) had inadequate antibody levels prior to the simulated postexposure booster. Five days after the postexposure booster, 27 of 29 (93%) had adequate antibody levels. The other 2 travelers were subsequently shown to have adequate VNA levels when tested 4 and 6 weeks later, respectively. CONCLUSIONS For travelers who were given pre-exposure ID HDCV vaccination within the last 2 years and received one IM postexposure booster dose of HDCV, most mounted an adequate early immune response. This data does not support a change in current recommendations for rabies PET in this group. Further research to ascertain the duration of protection of pre-exposure ID rabies immunization is required.