The aim of this study was to evaluate the effect of All-Trans-Retinoic Acid(ATRA) on acute promyelocytic leukemia (APM) patients with minimal residual disease. Two boys with APL, 4 and 6 years old, who were treated according to the POG 8101 protocol for 3 and 21/2 years respectively, achieved a complete remission confirmed by morphological, cytochemical and immunological characteristics of bone marrow after the end of treatment. The reverse transcriptase polymerase chain reaction (RT-PCR) revealed the presence of S type isoform of PML-RARa by analysis of PBMCs. Afterwards the patients received ATRA (45mg/m2/d per os) for 3 months, and 2 months later the disappearance of PML-RARa S fusion was established both by the analysis of PBMCs and by the analysis of BMMCs. In conclusion, RT-PCR is a technique for the diagnosis and assessment of APL minimal residual disease by amplification of the different PML-RARa. This technique may provide diagnosis in cases where conventional methods fail. Our results indicate that tretinoin is an effective agent for inducing complete remission in children with APL residual disease.