Syrian hamsters were injected with inactivated, attenuated, and virulent rabies virus (RV), and the antibody response was quantified by a neutralization test and the immunoglobulin class of the virus antibody was characterized by indirect fluorescent microscopy. Serum antibodies to RV were found to be predominantly of the immunoglobulin G2 (IgG2) class, although IgG1 anti-RV also were detected in high-titered sera obtained after secondary challenge. Brain extracts of hamsters inoculated intracerebrally with RV contained only IgG2 anti-RV. IgA and IgM anti-RV were not detected. The preferential IgG2 response to RV is in marked contrast to the isolated IgG1 response detected after inoculation of hamsters with soluble purified protein antigens.