La Crosse (LAC) viral antigen was detected in the skin of inoculated mice. Antigen was detected principally in the dermis of 102 of 120 (85%) mice with clinical signs of illness. To demonstrate the specificity of the fluorescence, LAC virus was isolated from selected samples and was identified by the complement-fixation test. Antigen was most often detected in skin rich in vascular and nerve tissue and was probably disseminated by hematogenous spread. Antigen was found in muscle, vascular, nervous, and other tissues of the dermis, depending on the age of the mice. Antigen was first detected in the skin of 80% of the mice (5 to 6 days of age) on postinoculation day (PID) 3. On PID 4, 100% of these mice were positive, but on PID 5, only 40% were positive, indicating that clearance or neutralization of antigen had occurred in peripheral areas. The skin biopsy technique may be applicable to diagnosis of arboviral infections in other vertebrates.