The effects of hypothalamic lesions on spontaneous and estrogen-induced LH release were studied in 17 female rhesus monkeys with regular menstrual cycles. In the cycle before surgery, all of the animals experienced 3- to 10-fold increases in serum LH and elevated (above 3 ng/ml) serum concentrations of progesterone. Three to 6 days after the onset of menstruation, lesions were made in the preoptic-anterior hypothalamic area (POA-AHA) in 14 monkeys by radiofrequency thermocoagulation (RF) or by the 180 degrees rotation of a modified "Halász" knife. About 35 days after surgery, the circulating levels of estradiol-17 beta (E2) increased to more than 200 pg/ml in each of the 14 monkeys. Three of the animals with RF lesions and 3 with knife lesions did not release LH or have elevated serum progesterone levels, an indication that they had not ovulated (effective). In 8 animals, 5 with RF and 3 with knife lesions, an LH surge and elevations in serum progesterone were observed (ineffective). After a 90-day postoperative period, the effective and ineffective lesioned groups and an additional group of 6 intact controls were given E2 to test further the ability of the hypothalamic-hypophyseal axis to release LH. The animals with effective lesions did not respond to increased E2 titers (200-400 pg/ml), but those in the ineffective and control groups showed an LH surge. Six to 11 months after surgery, histological examination of the brains from the animals with effective lesions revealed extensive bilateral destruction of the ventral POA-AHA. The suprachiasmatic nuclei or connections between these nuclei and the medial basal hypothalamus (MBH) were destroyed. In 2 animals, the supraoptic and ventromedial nuclei were partially damaged. In no instance was there damage to the paraventricular, dorsomedial, or arcuate nuclei. In animals with ineffective lesions, bilateral destruction of the POA-AHA was less extensive and most of the lesions were unilateral. Ovaries from animals with effective lesions contained small to medium follicles but luteal tissue was conspicuously absent. Spontaneous LH surges and elevated serum P occurred in 2 of 3 additional animals that had 270 degrees cuts around the MBH which left one anterior quadrant intact. Damage to the median eminence region was evident in the one animal that did not ovulate. These results suggest that in rhesus monkeys bilateral destruction of the ventral POA-AHA blocks spontaneous ovulation and compromises the ability of the hypothalamic-hypophyseal axis to release LH in response to estrogen.