Previously we have demonstrated that sperm counts of normal young men decreased during constant subcutaneous infusion of the LHRH agonist buserelin (118 or 230 micrograms/d). In order to test whether azoospermia can be achieved with higher doses, seven young men received 450 micrograms buserelin subcutaneously daily for 12 weeks via extracorporeal osmotic minipumps. To avoid symptoms of androgen deficiency, oral supplementation with 80 mg/d testosterone undecanoate (TU) was initiated in week 5 and was increased to 120 mg/d by week 8. Follow-up after treatment lasted for another 12 weeks. In order to evaluate possible psychotropic effects of treatment-related endocrine changes, continuous psychometric testing was performed focusing on personality, emotions and sexuality. After an initial rise, both serum LH and FSH returned to normal. FSH was below normal during the 3rd-5th week following treatment. LHRH stimulation tests performed at the end of treatment showed pituitary desensitization. Serum T (always measured between 0800 and 1300 h at least 12 h after last TU) tended to decrease by week 7 and remained slightly depressed until the end of treatment while libido, potency and emotional well-being remained unchanged. While testicular volumes showed a reduction from week 7 of treatment to week 10 post-treatment, sperm counts decreased only insignificantly from 65 +/- 10 to 44 +/- 14 million per ml in week 12 post-treatment. Severe oligo- or azoospermia was not observed in any of the seven men. It is concluded that full androgen substitution by TU can drastically delay if not abolish the antifertility effect of LHRH-induced pituitary desensitization.