The role of the Langerhans cells (LC) during HSV-1 infection in murine skin was examined. LC function as very potent antigen-presenting cells and represent the most peripheral immune cellular elements in the body. The footpad route was used to study the response of LC to infection with a pathogenic and non-pathogenic strain of HSV-1. Following infection with a pathogenic HSV-1 strain, there was an increase in the number of LC in the footpad skin. Depletion of LC from the skin by treatment with 10 per cent aqueous saline and abrasion led to the enhancement of HSV-1 virulence and the nonpathogenic virus became highly pathogenic. Progressive recovery of LC in the skin during the healing process was accompanied by a gradual increase in resistance to HSV-1 infection.