Twelve patients with acute lymphoblastic leukemia (ALL) were treated with aclacinomycin A (60 mg/m2/day for five days) and VP-16-213 (100 mg/m2/day). All were heavily pretreated and had relapsed or were refractory to primary or subsequent treatment. Eight patients were refractory to reinduction therapy given for first, second, third or fourth relapse. One patient was treated in third relapse; one in second relapse (after a short second remission) and two in first relapse-one with the Ph1 chromosome, after a four-month remission, and one patient who relapsed while receiving consolidation therapy. Four patients (33 per cent) responded, three entered complete remission (25 per cent), and one a partial remission (8 per cent). Two of the patients treated for refractoriness to reinduction therapy went into complete remission. Side effects from this treatment were similar to the conventional DAT regimen (daunorubicin, cytosine arabinoside, thioguanine), although the gastrointestinal toxicity and mucositis appeared to be more severe in this study population. One of the patients had severe ventricular arrhythmias which contributed to her death. The complete remission rate (25 per cent) in this group of very heavily pretreated ALL patients warrants further studies to evaluate these preliminary findings.