This investigation of experimentally produced osteopetrosis has produced evidence which suggests that the parafollicular cell is the source of an osteoblast-stimulating factor which is released during periods of hypercalcemia and which has a net effect on bone antagonistic to that of parathyroid hormone. This experimentally induced overproduction of an osteoblastic stimulus in infant mice results in hyperplasia of the osteoblastic endosteum, a dramatic increase in the capacity to incorporate 3H-proline into bone matrix, and an accumulation of bone producing osteopetrosis. Differentiation of this factor from thyrocalcitonin cannot be made on the basis of evidence Obtained to date.