ABSTRACT:The Till‐McCulloch spleen colony system was used to differentiate the time‐ and dose‐dependent effects of GPF (calf renal granulopoietic factor), ESF (erythrocyte stimulating factor) and Pyrexal (endotoxin from S. abortus equi) on the total and differential exocolonizing potential of treated donor mouse marrow cells. A single optimal dose of either hemopoietin given to the donor was found to activate transplantable colony forming units (CFU) of the hemopoietin‐specific cell line. There followed a series of time‐dependent oscillatory waves of specific CFU activation, the magnitude of which gradually dampened over a period approximating the stimulated cells’generation time. Flooding doses of GPF and ESF abrogated this phenomenon. Combination treatment with GPF and ESF cancelled out the cell line‐specificity of CFU stimulation, presumably due to the two hemopoietins’competition for a common stem cell. Multiple doses of GPF were found to potentiate the granulopoietic effects of a single dose of GPF, the response apparently being limited both by the magnitude of the stimulation and by the size of the available CFU pool(s). A single dose of Pyrexal failed to evoke a GPF‐like or ESF‐like CFU increase and shifted the marrow's differential exocolonizing potential in the direction of the erythrocytic cell line. The CFU response to GPF is thus qualitatively and quantitatively distinct from those evoked by ESF and endotoxin. The possibility is proposed that GPF may be specific for the granulocytic line at the level of the CFU compartment(s).