To assess the role of horses as amplification hosts during the 1993 and 1996 Mexican Venezuelan equine encephalitis (VEE) epizootics, we subcutaneously infected 10 horses by using four different equine isolates. Most horses showed little or no disease and low or nonexistent viremia. Neurologic disease developed in only 1 horse, and brain histopathologic examination showed meningeal lymphocytic infiltration, perivascular cuffing, and focal encephalitis. Three animals showed mild meningoencephalitis without clinical disease. Viral RNA was detected in the brain of several animals 12-14 days after infection. These data suggest that the duration and scope of the recent Mexican epizootics were limited by lack of equine amplification characteristic of previous, more extensive VEE outbreaks. The Mexican epizootics may have resulted from the circulation of a more equine-neurotropic, subtype IE virus strain or from increased transmission to horses due to amplification by other vertebrate hosts or transmission by more competent mosquito vectors.