Peritoneal macrophages transferred from adult CBA mice protected suckling syngeneic mice from intraperitoneal infection with herpes simplex virus. Macrophages from adult mice stimulated with proteose-peptone solution were more effective in providing protection than were unstimulated macrophages. The enhanced resistance provided by stimulated macrophages was associated with more efficient phagocytosis and intracellular destruction of virus, and with greater production of interferon. In contrast to the effects of stimulation on the adult mouse, the suckling mouse did not respond to proteose-peptone inoculation with the production of a population of macrophages that ingested more virus, produced more interferon, or more effectively destroyed virus.