We have developed a quantitative reverse transcriptase-polymerase chain reaction method for the quantitation of AML1-MTG8 transcripts in patients with AML-M2 and t(8;21) in different phases of the disease. Using this method, we have tested sequential samples from 13 patients to monitor minimal residual disease and were able to show a significant increase in AML1-MTG8 transcripts level in two patients 2 and 4 months before clinical relapse. In five patients tested at presentation and then sequentially at remission, we detected a marked decrease in the level of AML1-MTG8 transcripts as the treatment progressed. Patients in long-term remission of their disease had a level of up to 1 x 10(3) AML1-MTG8 molecules/microgram RNA. Two patients tested 2 and 4 months before hematologic relapse showed a level of 0.71 x 10(5) molecules/microgram RNA and this level increased further during relapse to 0.71 x 10(7) and 2.27 x 10(5) molecules/microgram RNA, respectively. Our results show that quantitation of AML1-MTG8 transcripts by competitive polymerase chain reaction is valuable in predicting early relapse in AML with t(8;21). Identification of at-risk patients may allow treatment to be modified to include additional or alternative therapy such as bone marrow transplantation.