Since age-dependent diminished macrophage function has been related to the increased susceptibility of newborn mice to herpes simplex virus (HSV) infection, the effect of several agents which might activate macrophages or other cells involved in immunity was investigated. BCG, typhoid vaccine, brucella vaccine, levamisole, or staphage lysate were administered to newborn mice prior to challenge with HSV-2. Of these agents, only BCG, administered ip or id 6 days prior to challenge, was found to increase the survival rate of newborn mice. The possible use of BCG, alone or in combination with other modalities, for the prevention or treatment of neonatal HSV infections is discussed.