Using a combination of intensive chemotherapy and G-CSF, we conducted a prospective trial designed to improve the complete remission (CR) rate in patients with AML evolving from a primary documented myelodysplastic syndrome (sAML) and therapy-related AML (tAML). Thirty-four patients (median age 61 years) with sAML (25 patients) or tAML (nine patients) entered the study. Induction course consisted of idarubicin (12 mg/m2 of body-surface area per day for 3 days) and intermediate-dose (ID) cytarabine in the 24 younger patients (1 g/m2 of body-surface area as a 2 h infusion every 12 h for 5 days) or standard-dose (SD) cytarabine in the 10 older patients (100 mg/m2 of body-surface area per day as a continuous infusion for 7 days), followed by G-CSF until neutrophil recovery or treatment failure. Nineteen patients (56%, 13/24 in the ID group and 6/10 in the SD group) achieved a CR (14/25 sAML and 5/9 tAML). Early death occurred in four patients, but four additional patients died in CR from treatment-related toxicity (overall toxic death rate 24%). Initial cytogenetics was available in 33 patients. The CR rate was significantly lower in patients with unfavorable cytogenetics compared to patients with intermediate cytogenetics (37% vs 79%). Median remission duration and overall survival were 3 and 9 months, respectively and not different between ID and SD patients. Although the treatment-related toxicity is high, a high CR rate can be obtained in these poor-risk AML patients with the use of intensive chemotherapy in combination with G-CSF, although the role of the latter is still to be proven. Results remain especially poor in patients with unfavorable cytogenetics. New approaches are needed to maintain remission in these high-risk AML patients.