The chromosomal translocation t (15; 17), hallmark of human acute promyelocytic leukemia (APL), has been shown to disrupt the retinoic acid receptor alpha (RARA) gene. Using a panel of probes covering the whole RARA gene generated in our own laboratory, we detected the gene rearrangement in 23 out of 25 cases of APL. It is conceivable that RARA gene rearrangement may serve as a highly specific marker of APL. The RARA gene configuration was investigated in two APL patients during the course of treatment with all-trans retinoic acid (ATRA). It was shown that phenotypically differentiated bone marrow myelocytes under ATRA therapy could still carry RARA gene rearrangement. This provides further evidence that ATRA induce complete remission of APL through differentiation induction of the leukemic cells.