Objectives To clarify the metabolism of ara-C to uracil arabinoside (ara-U, inactive form) and ara-CTP (active form) in vivo in patients with hematologic malignancies.Design & Methods ara-C was administered as iv inf for intermediate dose (1.0 g/m 2 ) and as sc bolus or continuous iv for low-dose therapy (3 10 mg/m 2 ). ara-C and ara-U levels were determined by HPLC or RIA (low dose). ara-CTP levels were measured by new combination method of HPLC and RIA.Results The plasma ara-C levels reached a mean peak value of 14.9 μg/ml by intermediate dose (107 ng/ml by low dose) and then rapidly declined, but plasma ara-U levels persisted. Even in intermediate dose the deamination process from ara-C to ara-U proceeded without saturation. There was a wide interpatient variability in ara-C but not in ara-U levels.In both dose the pharmacokinetic behaviors were essentially the same. Intracellular ara-CTP levels were detected even in low dose by new method and not necessarily correlated with the plasma ara-C levels.Conclusion The deamination process is crucial for ara-C pharmacokinetics. Determination of intracellular ara-CTP levels is essential to estimate the effect of ara-C.