Mechanisms of postinfectious pruritus and peracute death in mice by pseudorabies virus (PRV) were investigated by inoculating the Yamagata-S81 strain of PRV peripherally or intracerebrally into 4-week-old ICR and BALB/c mice. Clinical signs developed most rapidly in mice inoculated intracerebrally, with intermediate speed in mice inoculated intraocularly, and slowly in mice inoculated subcutaneously. Since intraocularly inoculated mice showed an acute reaction and this is considered a peripheral route, the distribution of viral antigens in the nervous system of intraocularly inoculated mice was examined immunohistologically. Viral antigens were mainly detected along the trigeminal and the oculomotor nerves, but neither necrosis nor an inflammatory response was observed in these areas. The infectious virus was efficiently recovered from the viral antigen-positive tissues. In the pruritic skin lesions, viral antigens were not observed. These findings indicate that the main route of viral spread in intraocularly inoculated mice is the trigeminal and oculomotor nerves and that the virus in the trigeminal nerve may trigger pruritus.