Different depot GnRH analogs (GnRH-A) are currently used for the reversible suppression of the pituitary-ovarian axis in several reproductive and neoplastic disorders in women. In spite of anecdotal reports of incomplete suppression by some depot GnRH-A, this issue has never been systematically investigated in adult women. Thus, we elected to study 40 normally cycling women with male-related infertility or benign reproductive disorders; each group of 10 subjects received a different GnRH-A for 3 months: buserelin (group B; 300 micrograms, sc, every 12 h, as a control), goserelin (group G; 3.6 mg, sc, every 28 days), leuprorelin (group L; 3.75 mg, im, every 28 days), and triptorelin (group T; 3.75 mg, im, every 28 days). Depot GnRH-A was administered by one of the investigators. GnRH tests (100 micrograms, iv) were performed before treatment (cycle day 7; test A) and on treatment days 57 (i.e. 1 day after the third depot GnRH-A; test B) and 84 (i.e. 28 days after the third depot GnRH-A; test C). Immunoreactive (i) LH levels were measured with an ultrasensitive immunochemiluminometric assay. Profound suppression of the iLH response to the GnRH test occurred in all subjects during treatment. Conversely, FSH levels in the third month of treatment tended to be higher in the depot GnRH-A groups than in group B, and this difference achieved statistical significance (P < 0.05) in groups G and L during test C. In GnRH test B, while the mean estradiol (E2) level was less than 75 pmol/L (< 20 pg/mL) in all group B subjects, individual E2 levels were greater than 75 pmol/L in five patients receiving depot GnRH-A (two in group G, one in L, and two in T). Finally, individual E2 levels during test C were greater than 75 pmol/L in only two patients of group G, who also reported vaginal spotting. Thus, we conclude that in adult women, 1) iLH was profoundly suppressed in the third month of administration of all GnRH-A tested; 2) FSH suppression with depot GnRH-A was less marked than that with high-dose short-acting sc buserelin; and 3) signs of an incomplete block of ovarian function can be present in the third month of depot GnRH-A administration, particularly when goserelin is employed.