We evaluated potential pituitary-adrenal influences on postoperative reticuloendothelial (RE) function. Male dogs, 13 to 18 kg (28.6 to 39.6 lb), were used and the operative procedure was hemicolectomy. The RE function was evaluated by a colloid clearance technique and circulating opsonin levels were quantified by bloassay. Normal animals manifested RE depression three hours following incision (49% decline in the global phagocytic index K and an associated 30% decline in the circulating opsonic activity). Dexamethasone sodium phosphate pretreatment over a three-day preoperative period prevented the postoperative RE clearance failure (control K = 0.69; postoperative K = 0.79) however, a slight (18%) but not significant decrease in opsonic activity occurred. Cortisone acetate or adrenocorticotropic hormone over a wide-dosage range manifested no depressing effect on in vitro phagocytosis. These studies, in conjunction with our previous findings of Kupffer cell activation following adrenalectomy, as well as the demonstration of opsonin depletion and RE phagocytic depression following surgery in the absence of the adrenal glands suggest that the pituitary-adrenal system modulates postoperative RE phagocytosis.