The mechanisms by which progesteroneand chlormadinone (6-chloro-Δ6-dehydro-17α-acetoxyprogesterone) block ovulationwere investigated. Electrical excitation of thebasal tuberal hypothalamus, intrapituitary ininfusionsof rabbit median eminence extract(MEE) or physiological amounts of exogenousLH were the ovulating stimuli used. Electricalstimulation (300 μA, 50 cps, 1 msec duration, 30sec on, 30 sec off) for 30 min with a single bipolarconcentric electrode implanted permanently intothe medial basal hypothalamus induced ovulationin 4 non-estrogen-primed, unanesthetizedrabbits with an average of 9.0 ± 1.6 rupturepoints/rabbit. These same 4 animals failed toovulate to this stimulus when either 2 mg progesteroneor 0.1 mg chlormadinone was injectedsc 16–18 hr prior to stimulation. Intrapituitaryinfusion of MEE over a 60–85 min period(equivalent to 2 ME/rabbit injected at the rate of 1 μl/min) induced ovulation in 24/26 controlanimals with an average of 7.8 ± 1.8 rupturepoints/ovulating rabbit, whereas 6 animals withcannulae outside the pituitary failed to ovulateafter similar treatment. Progesterone (2 mg sc15–20 hr prior to MEE infusion) completelyblocked ovulation in response to such intrapituitaryMEE infusion in 10/10 cases. Chlormadinone,in doses of 0.1, 0.2 and 0.5 mg sc, alsoprevented ovulation following intrapituitaryMEE infusion in 7/10, 8/9 and 4/4 rabbits, respectively,indicating a major blocking effectat the pituitary level. Pretreatment with progesteroneprevented the increase in 20αa-hydroxypregn-4-en-3-one (20α-OH) which normally occursduring MEE infusions, but did not alter thebasal output of 20α-OH nor prevent its increasefollowing a small stimulating injection of LH(0.5 μg/kg iv). On the other hand, when smallovulating doses of LH (4–5 μg/kg iv) were administered,pretreatment with progesterone orchlormadinone reduced the percentage of rabbitsovulating as well as the number of rupturepoints/ovulating animal. Our ovulation datasuggest, therefore, either that these progestogensexert some action at the ovarian level or thatthey counteract the facilitative-feedback effectof 20a-OH on LH discharge. (Endocrinology 84:277, 1969)