1-β-D-arabinofuranosylcytosine (ara-C) therapy (60mg/kg i. p. once daily) in mice causes a pronounced and rapid effect of short duration on the cytopoietic mechanism of the marrow. Of the blood elements, long-term effects were seen for the platelets. A striking effect of ara-C therapy was that of a hemoconcentration, which occurred early after treatment and was very temporary in nature. Being related to body weight loss suggests that this is due to dehydration, and not a hematological effect per se. In general, ara C’s hematological toxicity in the mouse has been found to resemble that reported in human studies. The finding that ara-C produces a cessation of normoblast production agrees well with its efficacy in the treatment of polycythemia vera and with erythrokinetic data. Although ara-C is known to rapidly induce megaloblastosis in man, no megaloblasts could be found in the marrows of mice treated with this agent, which agrees with other evidence indicating that the mouse is incapable of megaloblastosis. The pathogenesis of megaloblastosis is discussed in reference to ara-C’s capacity to produce an ‘unbalanced growth’. Deoxycytidine (100 mg/kg s. c. once daily), administered concurrently with ara-C, prevented all of the above effects of ara-C therapy. In the case of the platelets, however, a return to normal was, as compared to the erythroid and myeloid elements, somewhat delayed. The use of more drastic dosage schedules of ara-C, both for systemic and local tumor therapy, under continuous marrow protection with deoxycytidine, is recommended for furth