A novel action of leptin on bone formation has recently been described in animals. However, in humans, studies provide data, that, are less conclusive. So far, few studies investigated the leptin-bone density association in males. Moreover, it has been suggested that GH, IGF-1 and IGFBP-3 may be major players in the hormonal or paracrine pathways that regulate bone cell metabolism. Also, leptin has been shown to modulate the GH/IGF pathway. The aim of this study was to clarify further this issue by investigating (a) the influence of serum levels of leptin, GH, IGF-1 and IGFBP-3 on bone mass in various skeletal sites and, (b), the relationship between leptin and the GH/IGF axis. 363 healthy individuals were investigated. BMD and serum leptin, GH, IGF-1 and IGFBP-3 serum levels were assessed. Our results indicate that 11% of healthy males had bone density with T scores </=2.5 SD. No significant differences were found between men with normal and those with reduced BMD with regards to serum leptin, GH, IGF-1 and IGFBP-3 levels. A positive correlation was found between BMD and leptin levels in FN and T, and a negative one between leptin and IGF-1 levels. Further studies are needed before we reach final conclusions.