The objective of the thesis was the evaluation of the clinical tolerance of methotrexate (Mtx), administered in two high doses (2 g/m2 and 3 g/m2) in 218 children with acute lymphoblastic leukemia in 829 chemotherapy cycles. The assessment of the frequency and intensity of the most common adverse early effects of the therapy was keeping with the extended toxicity scale according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Tolerance of HD-Mtx was good, observed toxicities were not severe (most commonly of grade 1 and 2) nor prolonged. The most common early complications of the HD-Mtx therapy were: hepatic dysfunction, nausea and vomiting and infections, affecting 60%, 45-50% and 40-55% of patients, respectively. Based on the present investigations, the high risk group for severe early complications and toxicities of Mtx therapy included: patients with delayed Mtx elimination, children above 10 years of life and patients during the first HD-Mtx cycle.