SUMMARYThe mode of action is discussed of the peptide hormones which trigger neosynthesis of a specific product in their target cells without being involved in any release step. Particular attention is paid to the early events elicited by ACTH in isolated adrenocortical cells. It is shown that extracellular calcium ions at physiological concentrations can serve as first messenger activating steroidogenesis if the isolated cells are pretreated in an appropriate ionic environment. Among other factors the extracellular calcium/phosphate ratio seems to be of importance. A model is proposed where calcium serves as direct messenger in the physiological activation by ACTH, cyclic AMP being a subserving factor maintaining full steroidogenesis.