The objectives of this proposal are the synthesis of specific 5, 10-seco-19-norandrostane and cholestane derivatives, with acetylenic, allenic or olefinic functions in the 10-membered ring, and their evaluation as selective inhibitors of steroid-transforming enzymes. Some of the acetylenic and allenic ketones are designed as active site- directed irreversible inhibitors of delta 5-3-ketosteroid isomerase and testosterone 5 alpha-reductase, while allenic alcohols and allenic ketones are hoped to similarly inhibit 3- and (3- and 17)-hydroxysteroid dehydrogenases and the oxidative degradation of cholesterol. Others of the 5, 10-seco-19-norsteroids are hoped to be reversible inhibitors of these enzymes. Evaluation of inhibitors will be carried out with purified enzyme preparations, and compounds will also be studied in animals to determine hormonal or anti-hormonal activity.