Restraint stress suppresses the expression of MHC class II (I-A) glycoproteins by murine peritoneal macrophages. In order to evaluate the role of the pituitary adrenal axis, the effect of restraint stress on I-A expression by macrophages from adrenalectomized mice was evaluated. Adrenalectomy resulted in elevated levels of ACTH but abrogated the increase in corticosterone that results from restraint stress. The expression of I-A by macrophages from adrenalectomized mice was similar to that of sham operated mice or untreated mice. Adrenalectomy ameliorated the suppressive effects of restraint but the expression of I-A was below that of macrophages from adrenalectomized control mice. These results suggest that other factors in addition to corticosterone may effect I-A expression by murine peritoneal macrophages. A survey of other neuropeptides and catecholamines indicated that the addition of ACTH or epinephrine to macrophage cultures resulted in a suppression of I-A expression.