In this study, the clinical effectiveness of 5 drugs as combination chemotherapy, NCDVP (N:neocarzinostatin C: cytosine arabinoside D:daunorubicin V:vincrisitine P: prednisolone) and NCyclo-cDVP (Cyclo-c:cyclocytidine), for refractory acute leukemia was evaluated. Twenty patients (12 patients relapsed and 8 patients with the first induction failure) were entered in this study; 14 patients with acute non-lymphocytic leukemia (ANLL) and 6 patients with acute lymphocytic leukemia (ALL). Their ages ranged from 15 y.o. to 73 y.o. (median:39 y.o.) and the ratio of males to females was 15 to 5. Doses and administration methods were: N, 1,400u/m(2)/day, was administered by i.v. drip on day 3, 4, 5 and 6 and C, 40-80mg/m(2)/day, was administered by i.v. drip from day 1 to day 6. D, 20-25mg/m(2)/day, was administered by i.v. bolus on day 3 and 5 and V, 1.4mg/m(2)/day, i.v. bolus on day 2. P, 20-40mg/m(2)/day, was administered by i.v. drip or p.o. from day 1 to day 6. The treatment was repeated with at least a 7 days resting period. All patients were adequatedly treated and 9 of them, 45%, obtained complete remission (CR). One patient showed partial remission. On the basis of types of leukemia, 7 of 14 patients with ANLL, 50%, and 2 of 6 patients with ALL, 33%, achieved CR. In order to obtain CR, one or 2 courses of the treatment were required (median:1.4 courses) and the duration of CR ranged from 2 to 38 weeks (median:6 weeks). In peripheral blood, the nadir of white blood cell counts, neutrophils and thrombocytes was 600/cmm, 200/cmm and 24,000/cmm, respectively and the number of days to this nadir was 12 days for white blood cell counts, 11 days for neutrophils and 13 days for thrombocytes. The nadir of bone marrow nucleated cell counts was 7,800/cmm and the number of days to nadir was 10 days. As toxic manifestations, digestive side effects were marked, but were tolerable. Eight patients showed alopetia and 4 patients complained of pain in the parotid gland. One patient complained of a sense of numbness in the fingers. Toxic effects on liver function were recognized in 5 patients, one of whom died of fulminant hepatitis. The treatment of refractory acute leukemia is one of the major problems in the clinical management of leukemia. The results of the 5 drug combination chemotherapy presented here suggests its effectiveness in refractory acute leukemia in man.