The effects of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3 (1,25D), are mediated via the vitamin D receptor (VDR). 1,25D is known to have profound effects on bone resorption, but proof that the human osteoclast expresses VDR in vivo is absent. Receptors have been demonstrated in osteoblasts, and it has been generally accepted that the effects of 1,25D on formed osteoclasts are mediated via osteoblasts. Using conventional riboprobe in situ hybridization, VDR transcripts were readily detectable in osteoblasts within sections taken from normal bone and several actively remodelling bone tissues, namely, Paget's disease, renal hyperparathyroidism, and healing fracture callus. However, VDR transcripts also appeared to be present at low levels within osteoclasts from two pagetic samples and two hyperparathyroid samples. To examine this latter finding further, we have used the novel technique of in situ-reverse transcriptase-polymerase chain reaction (IS-RT-PCR) for specific amplification and detection of VDR mRNA within sections taken from the same conditions described above, and also from osteoclastoma samples. As expected, VDR transcripts were amplified and detected in osteoblasts and marrow cells, but were also prominently found in osteoclasts at approximately 50% of the level detected in osteoblasts in normal bone and at 60% in the active bone tissues. This suggests that in addition to effects on osteoclast precursors and those mediated via osteoblasts, 1,25D could exert direct effects on the active bone resorbing cells in vivo.