The LH and FSH responses to the administration of synthetic gonadotropin-releasing hormone (GnRH) were assessed in 14 patients with anorexia nervosa before, during and following weight gain. In 8 patients studied prior to therapy when they were at 53-64% of idal body weight, the LH response to GnRH was strikingly impaired while the FSH response was equal to that observed in normally menstruating women. After return to 79-88% of ideal body weight the LH response was improved but remained less than in the normal women. In a second group of 6 patients who were studied 4-11 months after hospital discharge when they were 90-94% of ideal body weight, the LH response was always equal to or greater than that found in the normal women. The serum estradiol concentration was low in all of the patients and remained less than 33 pg/ml even in those who returned to more than 90% of ideal body weight. Treatment with 25 mug of ethinyl estradiol for 3 days prior to repeat administration of GnRH did not result in a statistically significant increase of the LH or FSH responses above those before treatment. These data suggest changes occur in both hypothalamic and pituitary regulation of gonadotropin secretion in the course of nutritional rehabilitation of patients with anorexia nervosa and that synthesis and secretion of LH and FSH are modulated independently at the level of the pituitary gland.