The experience of 47 similarly-treated patients with acute lymphoblastic leukemia who developed hematologic relapse was reviewed to determine the effectiveness of reinduction therapy. The majority of patients were treated with a four-drug regimen utilizing L-asparaginase, vincristine, daunomycin, and prednisone. This regimen produced second, third, and fourth remissions in approximately 90% of patients, all of whom had experienced relapse while on chemotherapy. Eighteen percent of all patients who achieved second remissions are alive in prolonged second remissions, including four individuals who experienced relapse while receiving maintenance chemotherapy. These encouraging results underscore the efficacy of the four-drug regimen and emphasize the necessity for intensive treatment of recurrent acute lymphoblastic leukemia.