Treatment with interferon-alpha (IFNalpha) prolongs survival in chronic myeloid leukemia (CML). Additionally, cytarabine (AraC) can reduce the number of Ph + metaphases. Fortythree previously untreated patients with CML in chronic phase were randomly assigned to receive either. IFNalpha 2b (5 MU sqm/daily) or IFNalpha 2b in the same dosages plus monthly courses of low-dose AraC. The aim were complete hematologic remission at 6 months and cytogenetic response at 12 months. A complete hematologic remission occurred in 60.4% patients with single IFNalpha 2b in 76.2% patients with combination therapy. A cytogenetic response was present in 13.9% (major in 2 patients) with IFN therapy and in 38.1% patients with combination therapy. Two of 21 patients treated with IFNalpha/AraC therapy achieved major (9.52%), 4 partial (19.04%) and 2 minor (9.52%) cytogenetic response. Major side effects were cytopenia (20.1%), flu-like syndromes (42.4%) and increase of hepatic transaminases (3.4%). The side effects were more significant in the group receiving combination therapy. Based on published data that show a survival advantage for patients who achieved any cytogenetic response, and high rate of cytogenetic response which we observed in our study we believe that IFN plus AraC regimen could be a front-line therapy for CML.