In the present study, the possibility of calcitonin-induced self-inhibition in porcine thyroid slices was examined. Replacing the incubation medium at 5-min intervals during incubation and increasing the volume of incubation from 2 to 15 ml were observed to enhance calcium-stimulated calcitonin secretion in vitro. The authors gratefully acknowledge the generous supply of porcine thyroids by Mr. T. F. Andreskowski of Wilson and Co., and the technical assistance of Mrs. Patricia Reese. This study was supported in part by NSF Grant GB-43214.