To assess the function of the hypothalamic-pituitary-gonadal (HPG) axis in major depression, a multihormonal study was carried out in 20 depressed premenopausal women. Serum concentrations of LH, FSH, estradiol, progesterone, testosterone, and GnRH-stimulated LH and FSH were measured before initiation of treatment (on the first day after menstruation) and during clomipramine treatment (same time one menstrual cycle later). Significantly higher blood concentrations of testosterone were found in untreated patients compared to normal controls. Furthermore, there was a significant negative correlation between Hamilton depression scores and estradiol concentrations of patients. The efficacy of clomipramine treatment was not related to hormonal parameters.