Osteitis fibrosa, a part of the spectrum of renal osteodystrophy, is characterized by high bone turnover as a result of high circulating levels of parathyroid hormone (PTH). It is well accepted that the bone resorptive effects of PTH occur, at least in part, by inducing osteoblasts to secrete cytokines that stimulate both differentiation and activation of osteoclasts. One such cytokine, interleukin 6 (IL-6), exerts its actions via the IL-6 receptor (IL-6R), which has alpha and beta subunits. The alpha subunit binds IL-6 and exists in both membrane bound and soluble forms which can interact with the signal transducing components of the receptor or beta subunits and result in the same biological effect. Abnormalities in the IL-6 system have the potential to affect bone turnover and to modulate the effects of PTH. In this regard, we examined the levels of circulating soluble IL-6 receptor (sIL-6R) and plasma intact PTH in 27 patients on hemodialysis, of whom 15 were on therapy with vitamin D compounds and 12 were vitamin D naive. The results were compared to values obtained from 9 healthy controls. Blood samples were obtained pre-dialysis and sIL-6R levels were determined using a commercially available enzyme immunoassay, which measures biologically active sIL-6R. In patients on chronic hemodialysis, plasma levels of sIL-6R were 123.4 +/- 11.01 ng/ml. In healthy controls, the levels were 99.61 +/- 11.52 ng/ml, values not significantly different from those found in dialysis patients. PTH values ranged from 7-1,709 pg/ml in patients on hemodialysis; however, there was no correlation between intact PTH levels and the levels of sIL-6R. Similarly, vitamin D therapy did not influence the levels of sIL-6R. These data indicate that using an assay which is specific for biologically active sIL-6R, the levels of this receptor in patients on hemodialysis are similar to those found in normal individuals and neither the levels of PTH nor vitamin D therapy alter this aspect of IL-6 action.