Osteoclast-rich cultures were prepared by disaggregation of osteoclastomas (giant cell tumour of bone) and settlement onto glass or plastic surfaces. Autoradiography using [ 125 I]-salmon calcitonin ([ 125 I]-sCT) revealed specific binding only to multinucleate giant cells (osteoclasts) and a minor population of mononuclear cells. [ 125 I]-sCT competitive binding studies indicated a K(d) of 5 x 10 -10 M and receptor number of approximately 1 million sites/osteoclast. sCT treatment resulted in a dose-dependent rise in cAMP (EC 50 10 -10 M). Homogenates of an osteoclastoma also demonstrated specific binding of [ 125 I]-sCT. Chemical cross-linking of a labelled synthetic sCT derivative, [ 125 I]-[Arg 11,18 , Lys 14 ]-sCT, using disuccinimidyl suberate, resulted in labelling of a receptor component of approximate M(r) 85-90,000. The multinucleate giant cells (osteoclasts) of human osteoclastomas possess large number of CT receptors which exhibit the same binding kinetics and apparent M(r) as those of other CT target cells.