M icrotubule involvement in secretory events of the parathyroid gland was investigated in rats treated with colchicine and/or phosphorus, agents which have been shown to modify parathyroid secretion. Quantitative ultrastructural techniques were used in an effort to assess the cytoplasmic microtubule and secretory granule content of chief cells 3 h after treatment, when hypocalcemia was well established. After cochicine administration, the chief cells appeared to have lost all assembled microtubules and accumulated greater than normal amounts of cytoplasmic secretory granules. On the other hand, phosphorus treatment was associated with increased microtubule content although the cytoplasmic content of secretory granules remained unchanged. When colchicine and phosphorus were given concomitantly, microtubules were again absent, but the secretory granule content of the cells was markedly increased. These data provide direct evidence that colchicine disrupts assembled microtubules in chief cells of rat parathyroids; the consequence of this effect appears to be a blockage of hormone release which is reflected in the accumulation of secretory granules in the cell. The fact that microtubules also show a significant increase in content when hormone release from chief cells is presumed to increase, suggests that microtubules may participate in the physiological control of parathyroid hormone secretion.