Abstract Ten natural progestins were evaluated for their capacity to inhibit the in vitro motility of rat's uterus. Progestins with their ring A reduced in the 5β position were significantly more potent than Δ 4-3 keto and 5α reduced progestins. These last progestins were ineffective to inhibit uterine motility excepting 3α-hydroxy-5α-pregnan-20-one which was slightly less effective than progesterone. The potency of the progestins to inhibit uterine motility was related to their capacity to induce membrane stabilization. The data indicates that 5β, but not 5α reduction of progesterone, may be important for regulating myometrial activity.