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Summary. The effects of parathyroid hormone (PTH) on the size of the osteoclasts, nuclei, ruffled borders, and clear zones in long bones of thyroparathyroidectomized (TPTX) rats were quantitated as a function of time. These data were compared with the number of osteoclasts in the bone and with plasma calcium levels. A significant increase in the average size of the ruffled borders was demonstrated 30 min after injection of 50 U of purified bovine PTH, and of the clear zones 30-90 min after PTH. This was followed at 90 min by an increase in the average size of the cells. The sizes of ruffled borders and clear zones dropped sharply to control levels after 6 h, whereas the size of the cells remained elevated up to 12 h and returned to control values at 24 h. Plasma calcium levels were increased, but not significantly, between 30 min and 6 h. An increase in the number of osteoclasts was significant after 12 h. Removal of the parathyroid glands did not diminish the normal activity of osteoclasts. In animals with intact glands injection of 50 U of PTH did not cause a significant change in cell size or resorbing apparatus. It is concluded that PTH acts to rapidly stimulate the bone resorptive activity of osteoclasts and to cause a delayed increase in their number. Key words: Parathyroid hormone --Osteoclasts --Electron microscopy --Morphometry --Metaphysis.ruffled border in the osteoclast is the site of bone resorption. When descriptive electron microscopic techniques have been used, changes in the size of the ruffled border have not been noticed after exposure to PTH [1][2][3][4][5], although changes have been seen in response to calcitonin [6][7][8][9][10][11][12]. In a quantitative electron microscopic study, however, we found that the addition of PTH to cultured fetal rat bones activated the osteoclasts [13,14], resulting in an increase in the size of the cells in 3 h and an increase of the ruffled borders and clear zones in 1-6 h [14]. These effects were statistically significant long before an increase in the number of osteoclasts could be detected. We suggested that this effect on osteoclast activity might contribute to rapid osteoclast-mediated changes in calcium homeostasis. The recent finding that PTH causes a rapid activation of ruffled borders in intact egg-laying Japanese quails [15] supports this hypothesis.The purpose of this study was to quantitate the effects of PTH on osteoclasts in thyroparathyroidectomized (TPTX) rats. We found that injection of PTH in these animals caused early effects on the morphology of the osteoclasts. We also investigated the effects of endogenous PTH on osteoclasts, but found no difference between osteoclasts in TPTX and sham-operated rats. Methods