SUMMARY: Forty-two synthetic steroids have been studied for which certain relationships between chemical structure and progestational activity could be established. Thus, unsaturation and esterification in pregnane derivatives enhances progestational potency. Of the 4-dehydro derivatives, the 6α-CH3 and the 6α-fluoro compounds were the most active. Progestational potency on oral administration was increased in the 4-hydroxy derivatives. In the group with the 1:4-dehydro configuration, the basic activity of the parent compound was increased only by the introduction of a 6α-chloro or fluoro group. The 4:6-dehydro derivative showed an increase in potency on oral administration of about the same extent on introduction of a 6-chloro, a 6-fluoro or a 6:16α-dimethyl group. Only in the group of pregnane derivatives did changes of the parent molecule lead to a considerable increase in potency to inhibit ovulation. Since the maintenance of pregnancy in spayed animals is a parameter of progestational activity, it is felt that the results in animals are difficult to compare with those in female patients.