3 .alpha.-hydroxysteroid dehydrogenase (3.alpha.-HSD) plays a central role in the metabolism and action of steroid hormones and neurosteroids (steroids synthesized in the central nervous system). The high resolution structure of human type III 3.alpha.-HSD crystallized in complex with cofactor NADP is determined by X-ray diffraction. Furthermore the active site is determined. The structure coordinates of the enzyme may be used to design and select novel classes of modulators to human type III 3.alpha.-HSD.