By manipulating the rat's calcium balance, we have discovered that the calcium homeostatic system is a main regulator of cell proliferation in the bone marrow and thymus gland. Although the limits of the system's sphere of influence have yet to be completely defined, it is already known to include such diverse elements as chicken fibroblasts, liver parenchymal cells, and circulating small lymphocytes. Of even greater significance is the possibility that the ubiquitous cyclic AMP is calcium's partner and may even be the ion's intracellular agent for the control of cell proliferation. Thus, we now have a wide variety of possible explanations for diseases involving uncontrolled cell proliferation.