Kinetic and morphologic studies in patients with parathyroid disease, and a wide variety of studies in experimental animals indicate that one major effect of PTH is to increase the proliferation of osteoprogenitor cells into osteoclasts and so to increase bone turnover. PTH stimulates bone cells by increasing cell membrane permeability to calcium and consequently increasing calcium influx and by activating membrane-bound adenyl-cyclase. It is likely that the former event precedes the latter and that calcium is the second messenger and cyclic AMP the third messenger. PTH increases the production by bone cells of lactate, citric and carbonic acids, lysosomal enzymes, collagenase, and hyaluronic acid, some or all of which are concerned in the mechanism of bone resorption. With the exception of lactate which probably comes mainly from osteocytes, the increase in metabolic activity is largely due to the increase in the number of osteoclasts. There is also ultrastructural, biochemical, and biophysical evidence that PTH stimulates existing osteoclasts, but this most likely represents the transformation of inactive cells into an active state, and is a transient and nonsustainable effect. As yet, there is no evidence that either increased osteoprogenitor cell proliferation or increased osteoclast activity is mediated by adenyl-cyclase activation. PTH also acts on the deep osteocyte to cause rapid mobilization of calcium from the zone of hypomineralized metabolically active perilacunar bone. This effect is mediated by adenyl-cyclase activation and is preceded by a slight fall in plasma calcium probably due to the movement of calcium into bone cells. The function of this rapid hypercalcemic response to PTH is correct errors in the prevailing steady-state level of plasma calcium...