Nine Ph+ CML patients in chronic phase who were hematologically and/or karyotypically unresponsive to recombinant-IFN alpha 2a (rIFN alpha 2a) and neutralizing-rIFN alpha 2a Abs negative were shifted from rIFN alpha 2a to lymphoblastoid-IFN alpha (IFN alpha-Ly) therapy. After 3 months of IFNa-Ly treatment, the hematologic response was reinduced in 3 out of the 6 pts who were resistant to previous rIFN alpha 2a therapy, and was maintained in 2 out of 3 patients who were hematologically but not karyotypically responsive to rIFN alpha 2a. After 6 and 12 months, the hematologic response was progressively lost, being present only in 3 out of 7 and in 2 out of 3 evaluable patients respectively. None of the hematologically responsive patients achieved a karyotypic response (Ph neg. metaphases-0%). One patient, who was hematologically responsive, continued being treated with IFN alpha-ly for 36 months but he did not achieve any karyotypic response. The results of this study suggest that in the unresponsive and neutralizing-rIFN alpha 2a Abs negative CML patients a change in therapy, by using a non cross-reactive type of IFN alpha, would not be advantageous.