The role of macrophages in immunity against Marek's disease (MD) was studied. Chickens of one group were subjected to depletion of macrophages using repeated doses of Francil amorphous silica and those of another group were subjected to activation of macrophages using repeated doses of brewer's thioglycollate broth. Chickens of a third group were vaccinated with herpesvirus of turkeys FC 126 vaccine followed by depletion of macrophages. Chickens of these three groups, as well as groups of healthy unvaccinated and healthy vaccinated chickens, were challenged with virulent MD virus. A sixth group of healthy uninfected chickens was kept as a control. The results, based on clinical signs, gross and histopathological studies and agar gel precipitation test (AGPT) for antibodies, indicated that activation of macrophages enhanced immunity against MD and depletion of macrophages had the opposite effect. The protective effect of vaccination against MD was also lowered by depletion of macrophages. The results of AGPT indicated retardation of MD virus replication by macrophage activation and the reverse on depletion.