2-Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol (#8303) for children with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma in first relapse. Twenty-seven patients received one or more courses of DCF at 15 mg/m2/day as a 3-day continuous infusion immediately after achieving a second remission with a four-drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF. Hepatic toxicity, manifested by transaminase elevations, accompanied 62% of the courses. The median duration of the second complete remission was 4 months (range 2-16+ months), with only two of the 27 patients still in remission at 13+ and 16+ months. Plasma concentrations of deoxyadenosine (dAdo) and the ratio of red cell deoxyadenosine triphosphate to adenosine triphosphate (dATP:ATP) were measured prior to the DCF infusion and on day 4. A dATP:ATP ratio of 1.0 or greater was seen in two patients with acute renal failure. There was no apparent correlation between toxicity or response and the plasma dAdo concentrations. DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T-cell lymphoblastic malignancies.