To test the hypothesis that neuropeptide Y (NPY) is involved in the regulation of the estrogen/progesterone-induced luteinizing hormone (LH) surge in ovariectomized rats, we passively immunized animals against NPY by administering purified immunoglobulins raised against the peptide directly into the central nervous system. Ovariectomized rats were prepared with an intracerebroventricular (i.c.v.) guide cannula and an intravenous catheter prior to experimentation. On day 1 of the experiment the animals received a 5-microliters i.c.v. injection of a highly specific immunoglobulin against NPY (NPY-ab) and a 50-micrograms injection of estradiol benzoate. The antibody injection was repeated on days 2 and 3 of the experiment. On day 3, animals received a 2.5-mg injection of progesterone. Control animals were treated in exactly the same fashion except that a nonspecific control immunoglobulin was injected i.c.v. rather than the NPY-ab. As expected, the steroid-primed animals treated with the control antibodies exhibited large surges in LH secretion approximately 4 h following the progesterone injection. Concentrations rose from 4.2 +/- 1.0 to 27.9 +/- 9.9 ng/ml. In marked contrast, the NPY-ab-treated animals demonstrated no increase in LH concentrations. Baseline values were 3.1 +/- 0.3 ng/ml and remained unchanged (maximum concentrations were 3.8 +/- 1.9 ng/ml) following the progesterone injection. These results demonstrate that hypothalamic NPY plays a role in mediating the estradiol/progesterone-induced gonadotropin surge and suggests that this neuropeptide plays a physiological role in normal ovulatory surges of LH and FSH.