According to Selye and coworkers (1-3) overdosage of desoxycorticosterone acetate (DCA) in the rat may induce changes characterized by nephrosclerosis with hypertension and by cardiovascular and articular lesions of the "rheumatic type." On the basis of his experiments Selye (4, S) theorized that certain chronic diseases, such as rheumatic fever, periarteritis nodosa, arthritis, and hypertension, are the result of an abnormal response or of a perverted adaptation to stress mediated through the endocrine system, particularly an overproduction of adrenocortical hormones or hypercorticism. These conditions, which are all known to involve mainly tissues of mesenchymal origin, were therefore classified by Selye as "diseases of adaptation."Recently Taubenhaus and Amromin (6) reported that DCA stimulates the proliferation of fibroblasts and encourages the deposition of a homogeneous groundwork of collagen. They obtained these results by studying the effect of the hormone on the granulation tissue around subcutaneous turpentine abscesses in rats. On the basis of more recent studies (7) these investigators advanced the opinion that the stimulating effect of DCA may take place through mechanisms other than direct influence upon granulation tissue. The possibility that the action of DCA is mediated through an enzymatic mechanism must be considered especially in view of observations (8, 9) pointing to the important role of alkaline phosphatase in the proliferation of tissues of mesenchymal origin, and of other studies (10) indicating that DCA increases the activity of alkaline phosphatase in the epiphyses of rats' femora. The effect of DCA administration on other factors which influence mesenchymal cell proliferation, such as ascorbic acid metabolism and adrenocortical function, must also be considered in this respect.Previous unpublished studies from our laboratory (11) on the effect of large doses of DCA in intact guinea pigs showed that, as in the rat (4, 5), the main lesions attributable to this hormone are localized in the cardiovascular-renal system and in the adrenals. These changes consist of moderate to severe nephro-* The opinions expressed in this paper are those of the authors, and do not necessarily represent the official views of any governmental agency.