SUMMARY Parathyroid hormone has a direct effect on the osteoclast population present at the time of administration of the hormone. There was a significant stimulation of nuclear RNA synthesis at the earliest time (1½ hr.) at which the measurement could be made. This is followed by increased production of cytoplasmic RNA which reaches its maximum after a considerable time-lag (7 to 12 hr. after parathyroid extract (PTE)). The increase in cytoplasmic RNA is accompanied by a corresponding stimulation of protein and mucoprotein synthesis in the osteoclasts and the effect persists at least until 24 hr. This time-lag and the relatively long duration of the effect on protein synthesis can be correlated approximately with the effect on the plasma calcium level. It is suggested therefore that the rise in plasma calcium is mainly due to the increased cellular activity of the osteoclasts and the resulting increased bone resorption. The opposite effect on the osteoblast system has about the same time-sequence and would complement the effect on the osteoclast system. At about the same time as the maximum increase in cellular activity in the osteoclasts is observed, a significant effect on RNA synthesis in the endosteal mesenchymal cells, the precursors of the osteoclasts, becomes apparent. This is closely followed by a rise in the number of osteoclasts which is first apparent at 17 hr. after PTE and is maximal by 24 hr. Consequently, the rise in the number of osteoclasts is a secondary effect and is not responsible for the initial rise in plasma calcium which occurred much earlier. It is suggested that the increase in osteoclast numbers follows as a result of the increased metabolic activity of the osteoclast population present when the hormone was injected. There is a depression of RNA synthesis in both the osteoblasts and their precursors, the preosteoblasts. This means that the hormone has opposite effects, not only on the osteoblasts and osteoclasts, but also on their respective precursors, indicating that osteoprogenitor cells contain a mixture of cells with two main lines, those differentiating in an osteoblastic or osteoclastic direction, respectively.