Murine flank scarification with HSV-1 and -2 results in primary lesions at the site of inoculation within three days and lesions at secondary sites within four days. The severity of the infection can be given a numerical value or "score" which is derived from the number and size of these lesions. Using this model, we investigated the role of the epidermal basement membrane in HSV pathogenesis. We exposed murine epidermis to 5 x 10(4) plaque forming units of HSV-1 and -2, which by day 8 produced inoculation site (primary site) disease scores of 27 and 12.4 respectively, and secondary site disease scores of 29 and 30 respectively. In contrast, intradermal injection of HSV below the epidermal basement membrane did not cause disease. To determine if the basement membrane restricts HSV spread in vitro, Vero cells were cultured in the lower well of a dual well system. The upper well was separated from the lower well by a filter coated with the artificial basement membrane, matrigel. Addition of virus to the upper well failed to result in either viral accumulation in the lower well or infection of the cells in the lower well. These data suggest that the basement membrane is a barrier to the passage and spread of HSV.