Bone adaptation to mechanical load is accompanied by changes in gene expression of bone-forming cells. Less is known about mechanical effects on factors controlling bone resorption by osteoclasts. Therefore, we studied the influence of mechanical loading on several key genes modulating osteoclastogenesis. Human osteoblasts were subjected to various cell stretching protocols. Quantitative RT-PCR was used to evaluate gene expression. Cell stretching resulted in a significant up-regulation of receptor activator of nuclear factor-kappaB ligand (RANKL) immediate after intermittent loading (3x3h, 3x6h, magnitude 1%). Continuous loading, however, had no effect on RANKL expression. The expression of osteoprotegerin (OPG), macrophage-colony stimulating factor (M-CSF), and osteoclast inhibitory lectin (OCIL) was not significantly altered. The data suggested that mechanical loading could influence osteoclasts recruitment by modulating RANKL expression in human osteoblasts and that the effects might be strictly dependent on the quality of loading.