Adrenergic (alpha and beta), cholinergic (m and n) and gabanergic (gamma) influences on the regulation of basal hypothalamo-hypophyseal-adrenocortical (HHA) activity, as assessed by plasma cortisol levels, were investigated in non-stressed conscious cats. Alterations in neurotransmitter activities were induced by perfusing the cerebroventricles for 60 min with mock cerebrospinal fluid containing alpha, beta, m, n and gamma antagonists given along or in various combinations. Neither gamma, m nor n blockers altered basal HHA activity, whereas both alpha and beta blockers given alone or together, or combined with m, n and gamma blockers markedly elevated plasma cortisol. These responses were inhibited by the addition of dexamethasone to the perfusion fluid. These data suggest that basal HHA activity in the cat is maintained by a central inhibitory action of the adrenergic system on spontaneously discharging corticotropin-releasing factor neurons, and not via an adrenergic-cholinergic-gabanergic neural chain.