A prospective, randomized, double-blind study with crossover, using tamoxifen (TAM) (Nolvadex, ici Pharma, Missisauga, Canada) 20 mg/day and placebo (p) for 6 months each, was conducted in 16 infertile men with idiopathic oligozoospermia. Baseline sperm count was 17.092 +/- 3.09 (10(6)/ml). Hormonal profile was performed and included follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), thyroid-stimulating hormone (TSH), and luteinizing hormone-releasing hormone (LH-RH) stimulation tests. The sperm analysis and hormonal profile were repeated at 6 and 12 months of the study. A sperm penetration assay (SPA) was performed on zona-free hamster egg. Compared with the placebo group, the TAM group showed a significant increase in plasma FSH, LH, E2, and T levels (P less than 0.001), but not in PRL and TSH levels. However, LH-RH stimulation tests and SPA were found to be comparable in the two treatment groups, and there was no significant effect on sperm analysis. Tamoxifen appeared to be no more effective than the placebo in the treatment of idiopathic oligozoospermia.