Four patients with acute leukemias resistant to various ARA-C containing regimens and one patient with rapidly progressive malignant nonseminomatous tumor of the testis, who failed to conventional therapy were treated with HD ARA-C from december 1979 to september 1980. The drug was monitored by HPLC in plasma and in CSF. The first patient received only one course of HD ARA-C, developed fever and died of septicemia ten days later. The leucocyte count of her AML (FAB 2) decreased from 120,000/microliter to 30,000/microliter on the third day after HD ARA-C. Patient 2 reached CR criteria of the bone marrow for 23 days, then resistant AML (FAB 2) recurred. A male patient of 30 years was treated for recurrent acute undifferentiated leukemia (AUL) with a high cumulative dose of 176 gs of ARA-C. The repeated courses of treatment included a period of 50 days of CR. Toxicity was remarkable including pulmonal and cerebral dysfunction. A fourth patient with monocytic leukemia did not respond to HD ARA-C, neither did the patient with the malignant teratoma. Adverse reactions were tolerable. Only the third patient suffered from severe toxicity, pneumonitis, blurring vision, cerebral dysfunction and dermatitis. His pretreatment regimen had included X-ray prophylaxis to the skull. Since there was no possibility to prolong the remission duration in 1980, we decided not to treat further patients with HD ARA-C. Nowadays bone marrow transplantation offers some patients a capability of eradication of the leukemic disease.(ABSTRACT TRUNCATED AT 250 WORDS)