The long-acting opioid antagonist, naltrexone, stimulates LH and FSH in women during the early follicular phase of the menstrual cycle and is a new provocative test of hypothalamic-pituitary function (42,63). The acute effects of naltrexone (0.25, 0.50 and 1.0 mg/kg IV) on anterior pituitary (LH, FSH, PRL) and gonadal steroid (T or E2) hormones were studied in 7 female and 4 male rhesus monkeys (Macaca mulatta). Integrated plasma samples were collected at 20 min intervals for 60 min before and for 300 min after intravenous infusion of naltrexone over 10 min. In females studied during the early follicular phase (cycle days 1-3), naltrexone did not stimulate LH and significantly suppressed E2 (p less than 0.0003-0.0001) and FSH (p less than 0.006-0.0001). Naltrexone (0.50 and 1.0 mg/kg) also did not stimulate LH release in late follicular phase females (cycle days 10-12) when estradiol levels were in the peri-ovulatory range. FSH and E2 were significantly suppressed (p less than 0.01-0.05) after 1.0 mg/kg naltrexone, but not after 0.5 mg/kg naltrexone. However, in males all doses of naltrexone significantly stimulated LH (p less than 0.003-0.0001) and T (p less than 0.001-0.0001) but not FSH. LH increased significantly above baseline within 20 to 40 min and T increased significantly within 60 min. These gender differences in naltrexone's effects on pituitary gonadotropins and gonadal steroid hormones were unanticipated. These data are not concordant with clinical studies which report significant naltrexone stimulation of LH in men and in women during the early follicular phase.(ABSTRACT TRUNCATED AT 250 WORDS)