Six patients with acute nonlymphoblastic leukemia (ANLL) were treated sequentially with one subcutaneous (SC) injection (50 mg/m2) and one 156 hour continuous intravenous (IV) infusion (100 mg/m2/d) of 1-beta-D-arabinofuranosylcytosine (ara-C) with an interval of 12 hours. Leukemic cells were isolated from venous blood samples. The intracellular concentration of ara-C 5'-triphosphate (ara-CTP) was determined by high-performance liquid chromatography, and in two of the patients the plasma concentration of ara-C was determined by radioimmunoassay. A rapid biphasic elimination of the drug from plasma with an initial half-life of 18 minutes was seen after SC injection. After about 1.5 hours, the concentration was lower than that obtained at steady-state during continuous IV infusion. In the leukemic cells, the concentration of ara-CTP was higher after SC injection than during continuous IV infusion for about five hours. The mean half-life was 2.1 hours. Judging from the intracellular concentration of ara-CTP, considered to be the active metabolite, the results suggest that SC administration of ara-C can mimic continuous IV infusion if the dose interval is reduced from the traditional 12 hours to four to six hours. The results of this study emphasize the differences between the plasma pharmacokinetics of the parent drug and the concentration of the active metabolite in leukemic cells.