Does dehydroepiandrosterone act as an adrenal hormone in humans to maintain cortisol homeostasis by serving as a cortisol antagonist? If so, dehydroepiandrosterone might block the development of the diverse pathological processes potentiated by prolonged cortisol hyperactivity. And the plasma concentrations of total dehydroepiandrosterone and total cortisol, expressed as a C/D ratio, would have an important influence on the development of age-related pathology in diseases exacerbated by cortisol hyperactivity. Several major age-related diseases, designated as cortisol-potentiated diseases, belong in this category. The C/D concept predicts, other factors being equal, that the risk of initiation and progression of these diseases at all ages is directly related to the C/D ratio, individuals with elevated C/D ratios being at high risk.