Ten experiments utilizing 1,659 ewes were conducted to determine the potential of melengestrol acetate (MGA)-based treatments in inducing and synchronizing estrous activity in ewes during the nonbreeding season. In May or June, ewes were given .25 mg of MGA.ewe-1.d-1 or control diet and(or) a subsequent i.m. injection of zeranol, estradiol-17 beta, or oil vehicle. Fertile rams were introduced, and estrous and(or) lambing responses were determined. In Exp. 1, more (P < .01) ewes given MGA for 14 d followed by 5 mg of zeranol (i.m.) were in estrus than controls. Melengestrol acetate and zeranol independently induced estrus in Exp. 2, with MGA-treated ewes exhibiting the greatest lambing response (P < .05). The optimum duration of feeding MGA was 8 d vs 11 or 14 d (Exp. 3). In Exp. 4, as the dose of zeranol increased, synchrony of estrus increased but lambing response decreased. A dose of 1.25 mg of zeranol represented a compromise in estrous and lambing response and was determined to be optimally effective when given 54 h after the last feeding of MGA (Exp. 5). Shortcomings in lambing responses were treated in Exp. 6 by supplementing ewes with MGA after breeding, which proved unsuccessful, and in Exp. 7 by substituting estradiol-17 beta for zeranol, which proved effective when given 54 h after the last feeding of MGA (Exp. 8). In Exp. 9, use of MGA + estradiol increased (P < .05) the estrous and subsequent lambing response of 30-d postpartum ewes temporarily weaned of their lambs. In contrast, lambing response of 90-d postpartum ewes treated with MGA + estradiol was not increased by temporary removal of lambs (Exp. 10). These data collectively support the hypothesis that treatment of ewes with MGA + estradiol is an effective and practical approach for inducing and synchronizing a fertile estrus in ewes during the non-breeding season.