Accidental B virus (Herpesvirus simiae) infection of human beings working with macaques is frequently fatal. However, the pathogenic potential of other similar simian alphaherpesviruses, such as the squirrel monkey virus Herpesvirus saimiri (HVS1), is virtually unknown. As part of an effort to develop a murine model for infections with these agents, Balb/c mice were inoculated intramuscularly in the left hindlimb with 10 to 10(6) plaque forming units (PFU) of HVS1. After observation for clinical signs of infection for 21 days, mice were killed and specimens collected for serology and histopathology. Mice receiving 510(3) PFU of HVS1 exhibited severe, pruritic, ulcerative skin lesions near the site of inoculation and developed unilateral or bilateral hindlimb paralysis with severe muscle atrophy. Histological lesions were characterized by a necrotizing dermatitis and folliculitis. Spinal cord lesions consisted of a non-suppurative myelitis affecting primarily the ipsilateral dorsal horn of the thoracolumbar spinal cord with occasional extension to ventral and contralateral spinal cord regions. Immunohistochemical labelling confirmed the presence of viral antigen within the lesions, and anti-HVS1 IgG concentrations were related to the occurrence of disease. HVS1 infection in some mice extended from the ipsilateral dorsal horn and funiculus into the ventral and contralateral grey and white matter, resulting in bilateral hindlimb paralysis. Thoracolumbar spinal cord lesions resolved without continued spread of the virus to cranial nervous system structures, i.e., cervical spinal cord and brain., (Copyright Harcourt Publishers Ltd.)