Five women with amenorrhea of suprapituitary origin were given intravenous injections of 10 micrograms LH-RH every 90 minutes for 4 days by means of a portable infusion pump. Immediately before and after this, the LH and FSH responses to a test dose of 100 micrograms LH-RH were measured. Four days after discontinuation of the treatment, so that LH and FSH could be measured, blood was sampled every 10 minutes for a period of 6 hours, during which 20 micrograms LH-RH was injected intravenously every hour. Finally, a test dose of 100 micrograms LH-RH was given. The whole procedure was repeated at least 6 weeks later, but this time hourly injections of 100 micrograms LH-RH were given 4 days after discontinuation of the pulsatile LH-RH treatment. Four days after the pulsatile LH-RH treatment was stopped, increased LH and FSH responses to LH-RH were observed. These could be reduced by 6 injections, given hourly, of either 20 or 100 micrograms LH-RH. Although the totally released amount of both LH and FSH did not differ between the two treatment regimens irrespective of the LH-RH dose used, the response of both gonadotropins to the LH-RH test dose after the hourly 100 micrograms LH-RH injections was significantly lower. This indicated that desensitization can be attributed, at least in part, to a lower responsiveness of LH and FSH to LH-RH when pulsatile LH-RH is given. Low responses during treatment with pulsatile LH-RH could not be related to higher concentrations of plasma estradiol. We conclude that women with amenorrhea of suprapituitary origin who are treated with pulsatile LH-RH have a low state of responsiveness to LH-RH, which can be caused by the presence of the LH-RH and might be attributed in part to desensitization by LH-RH. Removal of the LH-RH results in an enhancement of the responsiveness, as the pituitary gland might have recovered from this desensitization.