The regulation of the proliferation of adrenocortical cells in culture is reviewed. The hormones and growth factors affecting adrenocortical proliferation in culture and their physiological relevance are discussed. The following general conclusions are made:(i) ACTH is growth-stimulatory in vivo, but directly replication-inhibitory both in culture and in vivo, and is therefore an indirect mitogen.(ii) Insulin, IGFs, some pituitary and brain growth factors, and other unknown factors in serum, stimulate growth in culture, but their role in control of adrenocortical size in vivo is unknown.(iii) Pure, known pituitary hormones, other than ACTH, have no effect on adrenocortical proliferation in culture.(iv) Angiotensin is mitogenic in culture and perhaps also in vivo under some circumstances.