It is now feasible to investigate bcr-abl transcription by the progeny of Ph-positive (Ph+) early and committed hemopoietic progenitor cells from patients with chronic myeloid leukemia (CML). Cells from individual colonies can be bisected and each half analyzed by cytogenetics or the reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect the bcr-abl transcript using internal nested oligonucleotide primers that flank the chimeric gene junction. We previously showed that some Ph+ colonies have undetectable PCR products for bcr-abl. When colonies are generated in the presence of alpha interferon (IFN-alpha) bcr-abl transcripts are undetectable in the majority of Ph+ colonies. These data suggest a potential mechanism for the action of IFN-alpha in Ph+ CML and indicate the need for a combined approach with cytogenetics and RT-PCR in analyzing the bcr-abl gene.