We studied the activity of endogenous opioid peptides in regulating LH secretion in patients with Turner's syndrome. To do so, we determined the LH secretory response to opiate receptor blockade by naloxone (0.08 mg/kg BW, iv) in 17 patients (age range, 9-23 yr). Eight patients were untreated (3 of whom had had spontaneous menarche), and 9 patients were taking ethinyl estradiol/medroxyprogesterone acetate treatment (5 of these patients were also studied before treatment). In addition, the plasma LH responses to GnRH (50 micrograms, iv) and placebo were determined in the patients as well as in 13 age-matched normal girls (6 prepubertal and 7 pubertal). Naloxone did not increase plasma LH levels in the amenorrheic untreated and treated patients with Turner's syndrome. However, in the 3 patients who had had spontaneous menarche and in normal pubertal girls naloxone increased plasma LH levels. GnRH was effective to the same extent in the patients and normal subjects. These results indicate that in patients with Turner's syndrome the opioidergic inhibition of LH secretion is impaired and is not restored by gonadal steroid replacement therapy. Moreover, the normal plasma LH responses to naloxone in the spontaneously menstruating patients with Turner's syndrome indicate both the clinical variability of this syndrome and the participation of endogenous opioid peptides in the regulation of normal menstrual function.