Mice were used to examine how the administration of adrenaline modulates the host defense system. The levels of granulocyte and lymphocyte subsets, including extrathymic T cells, were identified by immunofluorescence tests. When mice were continuously administered with adrenaline (400 mu g/mouse/week) by a diffusion pump for 1 week, the numbers of mononuclear cells yielded by the liver, spleen, and bone marrow were relatively stable but that yielded by the thymus decreased on day 7. The proportion of granulocytes, especially in the bone marrow, and the proportion of CD3(int) cells (extrathymic T cells) in the liver and other organs increased. By a single intraperitoneal injection of adrenaline (20 mu g/mouse), the acute response within 24 h was also examined. The number and proportion of granulocytes in the bone marrow decreased while those in the blood increased. It is presumed that the major result of the acute response is a migration of granulocytes from the bone marrow to the circulation. Concerning the similarity of responses between the administration of adrenaline and the previously reported results of excessive administrations of nonsteroidal anti-inflammatory drugs or calcitonin and from restraint stress, this raises the possibility that all these stimuli, which induce the activation of granulocytes and extrathymic T cells, are mediated via the production of catecholamines as a result of sympathetic nerve strain.