Studies were performed with three grey collies to determine whether a protracted demand for neutrophils resulting from daily endotoxin injections would influence their cyclic hematopoiesis. In each case, the characteristic profound oscillations of the neutrophil blood count were eliminated during a 1 - or 2-mo course of endotoxin treatment and were restored rather promptly upon cessation of treatment. In contrast, reticulocyte cycling generally tended to persist, although at a reduced rate. However, during the immediate postendotoxin period, there was a sharp rise in reticulocyte count without a readily discernible cycling pattern in the two grey collies that had Received the higher average daily endotoxin doses. Thus, the reticulocyte data did not conform to expectation based on the assumption that a peripheral neutrophil feedback provided the alternating competitive pressure for production of one or another blood cell type by a functionally restricted stem cell pool. It is possible that cyclic hematopoiesis in the grey collie may be inherent in the nature of the stem cell defect per se, e.g., an abnormality of the mechanism governing the transition to neutrophil commitment could lead to an oscillating committed stem cell compartment with a resulting regularly recurring competition for pluripotential stem cells. The effects of endotoxin in the grey collie can be understood within this postulated framework.