Several studies suggest that leptin modulates hypothalamic-pituitary-gonadal axis functions. Leptin may stimulate release of gonadotrophin releasing hormone (GnRH) from the hypothalamus and of gonadotrophins from the pituitary. A synchronicity of luteinizing hormone (LH) and leptin pulses has been described in healthy women and in patients with polycystic ovarian syndrome, suggesting that leptin may modulate the episodic secretion of LH. However, it has not been established whether LH regulates the episodic secretion of leptin. To further examine LH-leptin interactions, we studied the episodic fluctuations of circulating LH and leptin in two patients with Kallmann's syndrome (KS) before and on day 7 of pulsatile GnRH administration, and compared these with those observed in the early follicular phase of 10 regularly menstruating women divided into two control groups according to the body mass index of each patient. To assess episodic hormone secretion, blood samples were collected at 10 min intervals for 6 h, before and on day 7 of GnRH administration in KS patients, and during days 3-7 of the follicular phase in normally cycling women. LH and leptin concentrations were measured in all samples. For pulse analysis, the cluster algorithm was used. Before treatment, an apulsatile pattern with no endogenous LH pulsations was observed in both KS patients. However, leptin pulses were assessed in both women. During GnRH administration, pulsatile LH activity was achieved in both patients with pulse characteristics similar to those of the respective control group. Serum leptin concentrations and leptin pulsatile patterns were not modified. These results suggest that circulating leptin is probably not modulated by pulsatile GnRH-LH secretion.