The direct pituitary effects of estrogen and progesterone on the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were studied in ovariectomized (OVX) ewes in which the pituitary had been disconnected surgically from the hypothalamus (hypothalamo-pituitary disconnection, HPD). Gonadotropin secretion was restored with hourly pulses of 500 ng gonadotropin-releasing hormone (GnRH) via intra-atrial cannulae. Intramuscular injections of 50 µg estradiol benzoate (EB) to 5 sheep initially caused reductions (∼5O%) in plasma LH baseline, peak values and LH pulse amplitude. Therafter all parameters of plasma LH concentration increased 2- to 3-fold above starting values. After these 5 sheep had received 2 subcutaneous progesterone implants (mean ± SEM plasma levels 5.3 ± 1.5 nmol/1), the biphasic LH response to EB was still apparent and increases in LH peak values (267 ± 19%) and LH pulse amplitudes (262 ± 23%) were greater (p < 0.05) than those seen with EB alone (195 ± 11 and 172 ± 14%, respectively). The presence of 2 progesterone implants alone did not change plasma LH baseline, peak values or pulse amplitude, or plasma FSH values. In the second experiment, where 4 OVX-HPD ewes were given 4 progesterone implants (plasma progesterone 27.7 ± 3.4 nmol/l), there were no effects on basal plasma LH or plasma FSH values. The LH responses to EB were more marked in 4 OVX-HPD ewes given 4 progesterone implants than in the animals given EB alone. Also, the estrogen-induced LH surge occurred earlier in the ewes given 4 progesterone implants than in those given estrogen alone. The addition of 2 or 4 subcutaneous progesterone implants did not affect estrogen-induced suppression of FSH secretion in GnRH-pulsed OVX-HPD ewes. These data indicate that estrogen has a direct pituitary effect to influence the action of GnRH and that progesterone alone does not influence the secretion of LH or FSH by a direct pituitary effect. Progesterone may enhance the feedback effects of estrogen on LH secretion by a direct action at the pituitary level.