In the present study the effects of insulin, glucocorticoids and thyroid hormones on macrophage metabolism and function were investigated. The maximum activities of hexokinase, glucose-6-phosphate dehydrogenase, glutaminase and citrate synthase were determined in macrophages obtained from hormonetreated rats and those cultured for a period of 48 h in the presence of hormones. Macrophage phagocytosis was markedly inhibited by dexamethasone and thyroid hormones, remaining unchanged when insulin was added to the culture medium, however. The changes in the enzyme activities caused by hormone treatments of the rats were very similar to those found in culture. Insulin enhanced citrate synthase and hexokinase activities and diminished those of glutaminase and glucose-6-phosphate dehydrogenase. Dexamethasone had a similar effect except on glucose6-phosphate dehydrogenase. The addition of thyroid hormones to the culture medium raised the activities of glutaminase and hexokinase and reduced that of citrate synthase. The results presented support the suggestion that the effects of insulin, glucocorticoids and thyroid hormones on immune and inflammatory responses could well be mediated through changes in macrophage metabolism..