SUMMARY A search has been conducted for specific, 5α-dihydrotestosterone-binding proteins in a wide variety of tissues and cells upon which androgenic steroids have pronounced morphological and biochemical effects. High affinity binding proteins of this nature have been identified in cytoplasmic and nuclear extracts from a diversity of accessory sexual glands of many species, mouse kidney, testis and certain experimental androgen-dependent tumours. They are notably absent in most types of skeletal muscle and in soluble extracts prepared from prokaryotic organisms. The implications of these findings to the mechanism of action of androgenic steroids are discussed. While the selective binding of 5α-dihydrotestosterone indubitably plays a role of paramount importance in the mechanism of action of androgens in many accessory sexual glands throughout life, this process may be of importance in other tissues only during the period of early growth and development. A severe limitation to the importance of the binding of 5α-dihydrotestosterone in certain adult tissues is imposed by the very low activity of the enzyme, 5α-reductase, responsible for the formation of 5α-dihydrotestosterone.