Prostaglandin (PG) F₂α, is luteolytic in ewes, but the exact mechanism for this effect is not clear. 6α-Methyl-17α hydroxyprogesterone acetate (MPA) reduces uterine secretion of PGF₂α, but it does not interfere with luteolysis. The mechanism by which MPA suppresses PGF₂α and permits luteal regression remains to be determined. Three experiments were conducted to determine whether MPA reduces PGF₂α in uteroovarian blood, causes the release of PGF₂α before d 14 of the estrous cycle, or increases sensitivity of corpora lutea (CL) to exogenous PGF₂α. In Exp. 1 and 2, blank (control) or MPA-impregnated pessaries were inserted six days after estrus (i.e., d 6). Jugular, vena caval, and(or) uteroovarian blood samples were collected frequently (i.e., at .5 h intervals during twice daily collection periods of 2 h each) before and after luteolysis. The MPA reduced (P < .05) jugular, vena caval, and uteroovarian concentrations of PGF₂α, but MPA did not affect the interval from estrus to the first day of luteolysis. Average PGF₂α concentrations in uteroovarian and vena caval blood differed (P < .05) but the profiles did not. In Exp. 3, blank (control), MPA-impregnated, or no (untreated) pessaries were inserted on d 7. A minimal luteolytic dose of PGF₂α (Lutalyse ®; 4 mg/58 kg of body weight) was administered on d 8 or 12, blood samples were collected and the CL were collected 48 h after PGF₂α treatment. The MPA increased the sensitivity of CL to exogenous PGF₂α. Progesterone and CL weights were less (P < .05) in MPA-treated ewes than in control and untreated ewes given PGF₂α on d-8. The MPA-treated ewes given PGF₂α on d-12 had smaller CL than did ewes in the other two groups, but MPA did not affect progesterone concentrations. In summary, MPA reduces the ability of the uterus to secrete PGF 7a and increases the sensitivity of CL to a minimal luteolytic dose of PGF₂α. This information should improve our ability to control the estrous cycle ewes. / Master of Science