Although 2'-deoxycoformycin (dCF) has been reported in clinical trials to be less effective against myeloid than lymphoid malignancies, it may be useful for treating monocytic leukemia with the aid of 2'-deoxyadenosine (dAd) analogs. In the presence of 10 microM dAd, the concentration of dCF required to inhibit the viability of monocytoid leukemia cells was much lower than that required on normal or non-monocytoid malignant cells in primary culture. Among the dAd analogs, 9-beta-D-arabinofuranosyladenine (AraA) was also effective in combination with dCF. Although dCF alone slightly but significantly prolonged the survival of mice inoculated with U937 monocytic leukemia cells, combined treatment with dCF and AraA markedly prolonged the survival. These results suggest that the combination of dCF and AraA may be useful for the clinical treatment of acute monocytic leukemia.