The antineoplastic effects of 5-aza-2'-deoxycytidine (5-AZA-CdR) and retinoic acid on human HL-60 myeloid leukemic cells were investigated. 5-AZA-CdR or retinoic acid reduced the clonogenicity and induced the differentiation of HL-60 leukemic cells. The effects produced by 5-AZA-CdR and retinoic acid in combination on clonogenicity and differentiation of HL-60 leukemic cells were additive. These agents in combination also produced an additive decrease in the mRNA expression of the c-myc. These data indicate that 5-AZA-CdR and retinoic acid in combination produce an additive antineoplastic effect against HL-60 human myeloid leukemic cells.