The plasma levels of pituitary hormones (LH, FSH and prolactin) as well as testosterone were determined in 62 patients treated with combined therapy using the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide and the antiandrogen Flutamide. Plasma radioimmunoassayable LH and FSH levels increased to 534% (p less than 0.01) and 150% (p less than 0.01) of control, respectively, during the first 5 days of treatment, while, afterwards, a marked inhibition was observed which remained constant at approximately 30-50% of control values during the whole period of treatment. All patients showed a decrease of plasma testosterone concentration to approximately 10% of control levels. Detailed determinations of plasma testicular and adrenal steroid levels were then performed in 15 patients. Our data indicate that, except for the blockade of testicular 17-hydroxyprogesterone secretion, the combined therapy has no effect on plasma C-21 steroid levels. However, adrenal C-19 steroids, namely dehydroepiandrosterone and its sulfate, androst-5-ene-3 beta, 17 beta-diol and androstenedione were decreased to approximately 50% of control values (p less than or equal to 0.01). The main testicular steroids, testosterone and dihydrotestosterone, which were increased during the first 10 days of combined administration, rapidly decreased and reached approximately 10% of control values at later time intervals. The present study extends our previous observations indicating that the combined antihormonal treatment affects both testicular and adrenal steroidogenesis. Moreover, we have demonstrated that, up to at least 2 years, this treatment, in addition to decreasing the serum levels of testicular androgens, causes an inhibition of the plasma levels of C-19 steroids from adrenal origin.