Most of our knowledge of the physiological control of aldosterone secretion is based on animal experiments and clinical studies which were carried out in the 1950s and early 1960s by a large number of inspired, ingenious and meticulous researchers. Their work has been excellently reviewed by-among others-MULLER (1963), BLAIR­ WEST et al. (1963), LARAGH and KELLY (1964), GANONG et al. (1966), MULROW (1966), DAVIS (1967) and GROSS (1967). According to the majority of these investigators, aldosterone secretion is primarily regulated by the renin-angiotensin system, with plasma sodium and potassium levels and pituitary secretion of ACTH playing important secondary roles. During the last six years, this hypothesis has been generally accepted and has only occasionally been challenged. The following is an attempt to take-from the perspective of a relatively simple in vitro model-a new look at the efferent axis of the apparently very complex control system maintaining adequate aldosterone production in the mammalian organism. My views are based mainly on a series of experiments which I have performed in order to study more closely the interactions of adrenocortical tissue with substances capable of directly influencing aldosterone bio­ synthesis.