Sulfated glycoprotein-2 (SGP-2) is secreted in Sertoli cells and epididymal epithelial cells and plays important roles in the regulation of spermatogenesis and sperm maturation. To investigate whether endocrine disruptors affect spermatogenesis through an SGP-2-dependent mechanism, daily oral doses of testosterone (50, 200 and 1,000 microg/kg), flutamide (1, 5 and 25 mg/kg), ketoconazole (0.2, 1, 5 and 25 mg/kg), diethylhexylphthalate (10, 50 and 250 mg/kg), nonylphenol (10, 50, 100 and 250 mg/kg), octylphenol (10, 50 and 250 mg/kg), diethylstilbesterol (10, 20 and 40 microg/kg) or corn oil (control) were administered to 5 week-old, male Sprague-Dawley rats for 3 weeks. Following treatment with these endocrine disruptors, testicular expression of SGP-2 mRNA was analyzed using reverse transcription-polymerase chain reaction. Compared with the control, the lowest dose of testosterone (50 microg/kg/day) significantly increased expression of SGP-2 mRNA, whereas 200 and 1,000 microg/kg/day testosterone significantly decreased the expression (P<0.05). Flutamide, ketoconazole, diethylhexylphthalate, nonylphenol, octylphenol and diethylstilbesterol significantly decreased SGP-2 mRNA expression in testes at all doses studied, with the exception of 1 mg/kg/day flutamide (P<0.05). These results suggest that endocrine disruptors might decrease spermatogenesis in testes by decreasing expression of SGP-2 mRNA.