This paper describes a method for the direct measurement of human sRANKL (receptor activator of NF-kappaB ligand), a cytokine of the tumor necrosis factor superfamily, which is a key player in bone metabolism. Its role in the regulation of osteogenic disorders such as osteoporosis, Paget's disease and rheumatoid arthritis is being extensively discussed in the literature at present. We developed a highly specific, simple and reliable ELISA which allows the direct measurement of uncomplexed sRANKL in human serum. Assay characteristics such as analytical precision, sensitivity, interfering factors, sample stability and dilution linearity are shown. Reference values from healthy volunteers (n=57) were found to be between 0 and 2.7 pmol/l (10th-90th percentile) with a mean serum value of 1.3 pmol/l (median 0.9 pmol/l).