STI 571 and *IFN are the two single most effective agents for the treatment of CML. Their mechanisms of actions are different. Their toxicity is also different, but both spare normal hemopoietic stem cells. STI 571 is well tolerated, while conventional *IFN is poorly tolerated, especially in the elderly. PEG *IFNs are going to substitute for conventional *IFNs because of a better pharmacokinetic and toxicity profile and because require less injections (once a week vs. once a day).Resistance to IFN (6-13) and to STI571 (29-34) occurs in vitro and in vivo, where it increases with time for IFN and is also expected to increase with time for STI571. STI571 and IFN have different mechanisms of action and it has been shown in vitro that the combination of STI571 with alfaIFN is more toxic than either agent alone against Ph positive cells (35-37). Therefore, a combination of STI 571 with a PEG *IFN is worth testing. A phase II, dose-finding, exploratory study is required to investigate feasibility, toxicity, safety and tolerability of the combination. In CML, PEG INTRON studies are more advanced than PEGASIS studies. These considerations provide the rationale for this phase II study of STI 571 and PEG INTRON in CML.