Background. Multi-systemic acute side effects occur, in response to intensive therapies that have been applied in childhood malignancies in recent years. Amifostine has rarely been used in the childhood cancers as a multisystemic protective agent for minimizing these side effects. Procedure. In this Study, the effectiveness of amifostine in combination with chemotherapy for childhood cancer treatment has been researched. Of 11 Subjects (2.5 months-17 years) 4 Subjects had leukemia, 4 had solid tumor, and 3 1 ad lymphoma. For these 11 subjects, 29 chemotherapy Courses were given in combination with amifostine, and 20 without amifostine. Their hematological, gastrointestinal and hepatic toxicity were evaluated according to the WHO toxicity criteria. Amifostine was given intravenously in a dose of 740 mg/m(2), one to three consecutive days depending on the chemotherapy regimen. Results. The hemoglobin, leukocyte, and platelet levels of the two groups were not statistically different. However, when comparing the Courses of the patients receiving the same medications at the same closes, in the group with amifostine, mean erythrocyte transfusion requirement was significantly reduced (P=0.025). In 31%, of the Courses with amifostine and 50% of the Courses Without amifostine, febrile neutropenia developed. Gastrointestinal system and hepatic toxicity Was Significantly reduced in the Courses with amifostine with respect to those without it (P=0.001). Vomiting, hypotension and nausea were the only side effects related to amifostine. Conclusion. Use of amifostine during the treatment of childhood cancers with intensive chemotherapy and/or radiotherapy significantly reduced the erythrocyte transfusion requirements of the patients as well as gastrointestinal and hepatic toxicity. Pediatr Blood Cancel 2009;52:829-833. (C) 2009 Wiley-Liss, Inc.