Although 5-fluorouracil induces relatively minimal thrombocytopenia in mice compared with antiplatelet serum, the ensuing rebound thrombocytosis is much greater. It also occurs several days later. Administration of 5-fluorouracil 24 hr after antiplatelet serum suppresses the increase in platelets produced by antiplatelet serum, while the subsequent thrombocytosis is indistinguishable from that produced by 5-flourouracil alone. It is concluded that the thrombocytosis that occurs after 5-flourouracil originates from a class of primitive stem cells, or early megakaryocyte precursors, which are not killed by the drug. Thrombocytosis occurring after antiplatelet serum is derived from more mature precursor cells, which are sensitive to 5-fluorouracil.