The influence of luteinizing hormone-releasing hormone (LH-RH) pulse frequency on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was studied in hypogonadotropic hypogonadal women. They received three regimens of 5 days of pulsatile LH-RH (5 micrograms/pulse) given at 30-, 90-, or 180-minute intervals, with at least 6 weeks between treatments. On day 1, LH and FSH increased in proportion to the LH-RH pulse frequency. After 5 days of treatment with the 30- and 90-minute intervals, LH was still elevated, but FSH had returned to pretreatment levels together with a decline of the FSH response. The LH response only declined during treatment with the 30-minute pulse interval. During each treatment, estradiol (E2) increased. Explanations for dissociation between LH and FSH secretion during treatment with higher LH-RH pulse frequencies could be: (1) desensitization of FSH rather than LH secretion on LH-RH; (2) a differential effect of E2 on LH and FSH; (3) nonsteroidal ovarian factors selectively regulating LH and/or FSH release.