Human colostral cells in combination with antibody were able to destroy Herpes simplex virus-infected cells (Antibody-dependent cellular cytotoxicity--ADCC) while demonstrating very low spontaneous (non-antibody mediated) cytotoxicity (SCT). The colostral cells involved in ADCC required a high effector to target ratio, were mononuclear, adherent and totally inhibited by latex particles. These results demonstrate that a subpopulation of human colostral macrophages can mediate ADCC against virus-infected target cells. The biologic implications of intact colostral cell ADCC and low SCT in regard to protecting the neonate from infection and maternal cell mediated gastrointestinal damage are discussed.