The kinetics of Herpesvirus hominis (Type 1) replication and lesion development in guinea pig skin were determined. The data indicate that lesion scores did not always reflect virus content. Virus replication was detected prior to appearance of lesions and maximum virus content preceded maximum lesion score. Lesions resolved slowly while virus content declined rapidly to an undetectable level. The utility of the guinea pig skin-herpesvirus model for the evaluation of ara-A and kethoxal was studied. Ara-A treatment at three dose levels suppressed lesion development and at the two highest dose levels lesion development was delayed. Lesion virus content, when determined during the period of maximum virus replication, was not affected by treatment. Kethoxal markedly suppressed lesion development and virus growth. Aspects of this experimental model typify cutaneous herpes simplex disease of man. Studies designed to further assess its utility for evaluating antiviral drugs seem warranted.