OBJECTIVE: Most patients with acromegaly require additional treatments after trans-sphenoidal surgery. Although traditional methods of treatment aim at suppressing GH hypersecretion from the pituitary tumor, recent studies on the use of the GH receptor antagonist have shown that targeting the action of GH on peripheral tissues may be more effective. Estrogens and the selective estrogen receptor modulator tamoxifen have been used previously to suppress circulating IGF-I levels in patients with acromegaly. Positive effects of raloxifene in women with active acromegaly have been reported recently. This study was designed to examine the potential role of raloxifene in the treatment of acromegaly in male patients. DESIGN: We studied eight men with active acromegaly despite the fact that they were receiving traditional treatments. All subjects were treated with raloxifene (60 mg twice a day) for a median of 5 weeks. METHODS: The effects of raloxifene on GH secretion were assessed by obtaining 24-h GH profiles and studying the response of GH to various stimuli before and after treatment with raloxifene. Serum IGF-I was measured before and after raloxifene treatment. RESULTS: Raloxifene did not affect basal GH secretion or response of GH to TRH, GHRH or glucose, but it decreased circulating IGF-I by 16+/-4% (P=0.001), and normalized plasma IGF-I in two patients. No changes in clinical parameters were observed. Prolactin levels, the prolactin response to TRH and free testosterone levels remained unchanged. Raloxifene was well tolerated. CONCLUSION: Raloxifene might be useful in the treatment of male patients with active acromegaly, but longer term studies are clearly needed.