1. Oestradiol 17 beta inhibits the rat myometrium but the role of progesterone is uncertain. We have examined the interaction of the two steroids in the control of uterine activity in pseudopregnancy and the oestrous cycle. 2. Progesterone reversed the oestradiol-induced inhibition of the myometrium in ovariectomized rats in vivo, but had little inhibitory effect of its own unless treatment was continued for several days. 3. The frequency and amplitude of intra-uterine pressure cycles was unaffected by pseudopregnancy, but during the oestrous cycle frequency fell abruptly during late dioestrous and did not recover until early oestrus. 4. It is suggested that oestradiol is the major regulator of myometrial activity during the cycle and that progesterone interferes with the action of oestradiol, thereby paradoxically increasing uterine activity.