The human leukemia cell line K 562, when treated with subcytotoxic doses of hemin, undergoes reversible erythroid commitment, as shown by the increased synthesis of hemoglobin. Hemin-treated cells maintain replicative capabilities, although perturbations in cell cycle kinetics are induced. K 562 cells were used to investigate changes in antitumor drug sensitivity as a consequence of cell differentiation induced by hemin treatment. K 562 leukemia cells, cultured in the presence of 20 microM hemin for 12 days, were treated with non-phase-specific (adriamycin, 4-OOH-cyclophosphamide, mitomycin C, bleomycin, cis-diamminedichloro platinum) and phase-specific (vincristine, methotrexate and 5-fluorouracil) antitumor drugs. The results obtained by chemosensitivity tests showed a generalized decrease in chemosensitivity of the K 562 cells to all the drugs tested as a consequence of the hemin-induced differentiation.