Ph chromosome occurs in nearly all patients with CML, and eliminating Ph-positive clone is a major target in the treatment of CML. IFN-alpha is a well-known effective treatment in chronic phase CML. The cytogenetic response and the prognostic factors in 128 CML patients treated with IFN-alpha were retrospectively studied. IFN-alpha administered singly at a dose of 3 million U/day for 2 - 3 times a week or in combination with either hydroxyurea (Hu), busulfan (Bu), low dose Ara-C or harringtonine. Karyotyping was examined by G-banding before and after IFN-alpha-based treatment. The results showed that all patients achieved complete hematological remission. Cytogenetic response occurred in 36 of 118 patients with standard t (9;22) translocation; 3 of these 36 patients had a complete cytogenetic response (Ph = 0), 13 had major cytogenetic responses (Ph < 35%) and 20 had minimal response (Ph > 35%). The total cytogenetic effectiveness was 13.6% (16/118). Four of seven patients with complicated variant translocation also achieved cytogenetic response, 2 of them had a major cytogenetic response and 2 had minimal response. Factors influenced the prognosis associated with cytogenetic response included sex, patient status at diagnosis and IFN-alpha administered singly or in combination with other chemotherapeutic agents. IFN-alpha could not prevent the progression of CML. It is concluded that Ph(+)CML patients with both standard and variant translocation had major cytogenetic response to IFN-alpha treatment at a dose of 6 - 9 million U/week in single or combination with Hu/Bu, however, IFN-alpha treatment could not prevent disease progression. Long term survival was also observed in patients with variant translocation treated with IFN-alpha. Regular cytogenesis examination in CML patients is necessary during IFN-alpha therapy, which is useful to reflect curative effect and progression of the disease.