OBJECTIVE: This study was undertaken to evaluate trends in the use of rabies postexposure prophylaxis (PEP) before, during, and following an epidemic of raccoon rabies in Massachusetts. METHODS: The authors reviewed initiation of PEP as reported to the Massachusetts Department of Public Health (MDPH) from August 1994 to December 1995 and surveyed hospital pharmacies to determine the number of vials of Human Rabies Immune Globulin (HRIG) dispensed from 1991 through 1995 and charges to patients per vial. RESULTS: PEP use increased dramatically, from 1.7 per 100,000 population in 1991 (pre-epidemic) to 45 per 100,000 in 1995 (after the first stages of the epidemic). The median costs per patient for biologics was $1646 (range: $632-$3435). Including physician and emergency room charges, per-patient median costs were $2376 (range: $1038-$4447). Total health care charges for PEP in Massachusetts in 1995 were estimated at $2.4 million to $6.4 million. CONCLUSIONS: Given the rapid increase in use of PEP, further studies should be undertaken to determine the appropriateness of use, and other alternatives, such as oral wildlife vaccines, should be considered.