Background. Sex hormones are important regulators of calcium and phosphate homeostasis. Estradiol appears to be a major determinant of bone health in the male gender. However, physiological effects of estrogens on calcium and phosphate homeostatic fluxes in men are still poorly understood.Objective. We investigated the influence of 6 weeks of the SERM raloxifene, an estrogen agonist in bone, but devoid of feminizing actions, on calcium and phosphate metabolism in healthy middle-aged men.Design. In a double-blind, randomized, placebo-controled, cross-over study, we evaluated the influence of 120 mg/day of raloxifene on calciotropic hormones levels, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption, as assessed by the calciuric response to an oral calcium load.Results. As compared to the placebo period, raloxifene treatment decreased the response to an oral calcium load, together with a decrease in 1,25(OH)2D3 and in IGF-I serum levels. Maximal renal tubular phosphate reabsorption was decreased in raloxifene-treated men following the calcium load. The renal handling of calcium was not changed.Conclusion. These results are compatible with the hypothesis that raloxifene is associated with lower IGF-I and 1,25(OH)2D3 levels, with consequently reduced intestinal calcium absorption capacity.