It was shown that rapid diagnosis of herpes simplex skin lesions by immunofluorescence techniques is a practical possibility in a routine hospital microbiology department. Scrapings and swabs were collected from 43 lesions of the skin and mucous membranes of 42 patients. Herpes simplex virus was isolated in tissue cultures from 21 of these lesions. Viral antigen was detected by immunofluorescence on scrapings from 15 of the 21 virus-positive lesions, and by immunofluorescence on inoculated tissue cultures from all 21 virus-positive lesions. Virus could be identified by immunofluorescence on tissue cultures 17 hours before cytopathic effect was detectable. No herpes simplex virus immunofluorescence was seen In scrapings or inoculated tissue cultures from 22 virus-negative lesions.