Evidence from several studies suggests that soy protein and/or its isoflavones may have beneficial effects on bone in postmenopausal women and animal models who have osteoporosis. The present study examined the dose-dependent effects of soy isoflavones in the context of soy protein or casein on the male skeleton. Thirteen-month-old male Fisher 344 rats were orchidectomized (ORX; 5 groups) or sham-operated (Sham; 1 group) and immediately placed on dietary treatments for 180 days. Diets were semi-purified and the protein source was either casein (Sham and ORX; controls), casein with two added doses of isoflavones (Iso1; 600 mg/kg diet and Iso2; 1200 mg/kg diet), soy protein with normal isoflavones content (Soy; 600 mg/kg diet), or soy protein with added isoflavones (Soy+; 1200 mg/kg diet). A 7% loss of whole body bone mineral density (BMD) was observed due to orchidectomy; however, the ORX induced BMD loss was significantly reduced to 4.3 and 4.7 % with the Soy and Soy+, respectively. Both doses of isoflavones in conjunction with casein also reduced the loss of whole body BMD, albeit not significantly different from ORX control animals. Trabecular bone histomorphometric analysis of the proximal tibia further supported the bone-sparing role of soy isoflavones as indicated by higher percent bone volume and trabecular number, and lower trabecular separation. We conclude that isoflavones exert modest beneficial effects on the male skeleton whether provided with casein or a soy protein.