Bone marrow cells from five patients with acute promyelocytic leukemia (APL) with t(15;17) were studied by a combination of fluorescence activated cell sorting and fluorescence in situ hybridization (FISH) to establish the cell lineage involvement of t(15;17). Interphase FISH demonstrated that the fusion gene (PML/RARA) was present in almost all abnormal promyelocytes. In one case, the translocation was demonstrated in both CD34+ and CD34- APL cells. The t(15;17) abnormality was not detectable in erythroblasts nor in T- or B-lymphoid cells. These results suggest that lymphocytes and erythroblasts are not clonally involved in APL, and that malignant transformation in some cases of APL may occur at the level of CD34+ cells.