Humoral factors which stimulate release of mature granulocytes from body reserves are presumed to be the mechanism through which high yields of granulocytes are obtained from donors by filtration leukopheresis. Postpheresis plasma (PPP) obtained 2 hr after leukopheresis, when infused into normal rats, induced a peak granulocytosis at 3 hr of 22,000/cu mm above controls. A substance in the nylon filters, which caused a peak granulocytosis at 4 hr of 7600/cu mm above controls, was eliminated by washing the filter with 30 volumes of saline. Injection of PPP obtained following leukopheresis with washed filters resulted in an 8000/cu mm increase in granulocytes. One milliliter of PPP given 1 hr before pheresis increased the granulocyte yield from 4.3 to 8.7 times 10–7 granulocytes in a 2-hr run. We conclude that (1) a humoral substance elaborated by the host during filtration leukopheresis induces a granulocytosis in the donor, (2) a substance in commercial leukopaks, which can be eliminated by vigorous washing of the filters, may be responsible in part for granulocytosis observed during leukopheresis, (3) PPP may be used to increase granulocyte yields in donors undergoing leukopheresis.