The mucosal immune system is the first line of defense for a broad range of pathogens that greatly impact humans and veterinary species. The respiratory tract is the entry site of many high morbidity and mortality animal viruses, including equine herpesvirus type 1 (EHV-1). EHV-1 is endemic in horse populations worldwide, causing respiratory disease and sometimes results in abortion in pregnant mares and the neurological disease, equine herpesvirus myeloencephalopathy. A successful mucosal immune response is crucial for protection and prevention of these severe outcomes.This dissertation focuses on mucosal immunity against EHV-1 and how it differs between non-immune horses that develop clinical disease, and immune horses that do not. The phases of the immune response are crucial in orchestrating this defense. The innate inflammatory response regulates the initiation of the anti-viral state, by either promoting inflammation in non-immune horses or driving the return to homeostasis in immune horses. The success of the two arms of the adaptive immune response determines whether viral replication and clinical disease occur. Mucosal secretion of neutralizing antibodies prevents viral replication in the upper respiratory tract and halts the virus at its earliest stage. EHV-1 specific T cells form a second line of defense in the peripheral blood and can localize to the upper respiratory tract when mucosal antibodies fail. T cells respond through production of IFN-γ and release of cytotoxic granules. The papers in this dissertation identify a mechanism for protection by the mucosal immune system during EHV-1 infection. They provide new insight on equine mucosal immunity, in healthy horses and during viral infection, and novel methods and reagents for the study of equine immune cells, both at mucosal sites and in the peripheral blood.