Equine rhinitis A virus (ERAV) is a member of the Aphthovirus genus, and has many physical and structural similarities to the prototype Aphthovirus foot-and-mouth disease virus (FMDV). The pathogenesis of FMDV has been extensively studied, however, the similarities in the pathogenesis of ERAV and FMDV disease has not been well documented. This study describes and compares the pathogenesis of ERAV both in the natural host and a small animal model alternative (CBA mice). Distinct parallels in the pathogenesis of the acute infection of these two viruses are described where infection in the upper respiratory tract precedes shedding of high levels of virus from the nasopharynx and a transient viraemic phase before dissemination to distal sites. The finding that ERAV is maintained at high levels in the urine of infected horses for at least 37 days post infection, however, is a feature unique to ERAV amongst all of the picornaviruses.