We investigated whether changes in iron metabolism and the transferrin receptor (TRF‐R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara‐C). Treatment with 100 n M ara‐C for 48 h reduced thymidine uptake and increased the surface expression of the TRF‐R on leukaemic blasts derived from 13/16 (81%) patients and on the HL‐60 and U‐937 cell lines. Whereas intracellular non‐haem iron was strongly depleted 24 h after ara‐C addition, TRF‐R up‐regulation and recovery of intracellular non‐haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara‐C and the iron chelator desferioxamine (DSF) on the growth of HL‐60 and U‐937 cells. We found that desferioxamine strongly potentiated the effects of ara‐C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara‐C and an iron chelator in terms of antileukaemic effects.