A study was made of the immunospecific lysis of mouse fibroblasts by rat lymphocytes sensitized in vitro against mouse cells in the presence or absence of macrophages. The cytolytic activity of rat lymph node cells decreased if they were filtered through a glass bead column prior to sensitization. This decrease could be reversed by the addition of defined amounts of peritoneal macrophages. The ratio of added macrophages to lymphoid cells was found to be critical. While small amounts of macrophages added within a defined dose range caused enhancement of activity, both of glass bead treated and of untreated populations, addition of higher quantities resulted in the inhibition of the reaction. A possible regulating role of macrophages in immune reactions is suggested.