Recent data indicate that leptin may well play an important regulatory role in the hypothalamo-pituitary-gonadal axis. In order to further unravel the mechanisms by which leptin acts, we have studied the effect of treatment (8 days) of leptin antiserum (5 microl daily; i.c.v.) on LH pulsatility and estrous cycle in adult female rats. The administration of leptin antiserum led to a marked decrease in LH pulsatility as assessed by the area under the curve (13.5 +/- 4.7 ng/ml) in comparison to rats treated with normal rabbit serum (114 f 53 ng/ml; p < 0.01). Furthermore, rats treated with leptin antiserum showed an impairment of reproductive function as shown by the fact that all rats remained in anestrus. In conclusion, these data show that leptin markedly influences LH secretion and the estrous cycle in the female rat.