Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders characterized by uni- or multilineage maturation defects of the bone marrow. Controversial therapeutic results have been obtained using growth factors or differentiating agents such as 13-cis retinoic acid. In this pilot study we evaluated the effects of all-trans retinoic acid (ATRA) in 10 MDS patients (5 male, 5 female). Six patients had refractory anemia (RA), 1 had refractory anemia with excess of blasts (RAEB), and 3 had refractory anemia with excess of blasts in transformation (RAEB-t). All patients received the same dose of ATRA (45 mg/sqm/day) orally for 6 weeks. A rise in hemoglobin concentration > 1g/dl was observed in 3/10 patients, while 5/10 patients showed an increase in granulocyte count > 0.5 x 10(9)/l without concomitant increase in the percentage of blast cells in the bone marrow. A rise in the platelet count > 50 x 10(9)/l was observed in 1/10 patients. All the effects were transient and maximal responses were obtained by the fourth week of treatment. Thereafter, the peripheral blood counts started to drop again, reaching pre-therapy values by the end of the treatment. This phenomenon could be attributed either to the exhaustion of an ATRA-responding cell pool, the development of cellular resistance to ATRA or to a reduction of plasma ATRA levels after prolonged treatment. According to our results, it seems that ATRA might have therapeutic efficacy in MDS, particularly if its effect could be improved by combinations with other differentiating agents or growth factors.