Monoaminergic influences on the regulation of the hypothalamo-hypophyseal-adrenocortical (HHA) system during acute stresses (hypoxia and hypercapnia) were investigated in male rats. Plasma corticosterone levels were used to assess HHA activity, and the alterations in monoaminergic activity were induced by pretreating the animals with various pharmacologic agents (reserpine, αMT, FLA-63, pCPA, L-Dopa, pargyline, Lilly 110140, phentolamine and propranolol). Dexamethasone-treated rats were utilized to assess the site at which these monoaminergic substances acted. The latter experiments showed that these agents did not have a marked effect directly on the adrenal cortex and thus the site(s) of action was at the level of the anterior pituitary and/or above. Altering the serotoninergic system did not appreciably influence the HHA response to hypoxia and hypercapnia, whereas increasing the activity of the adrenergic system partially prevented the rise usually observed in plasma corticosterone levels during these stresses. These data suggest that different aminergic pathways may be utilized for different stresses.