CD44 is a cell surface antigen that expresses on leukemia blasts from most acute myeloid leukemia (AML) patients. It has been reported that ligation of CD44 with some specific anti-CD44 monoclonal antibodies can reverse the differentiation blockage of leukemia cell lines. In this study, the differentiation and apoptosis-inducing effects of HI44a, another anti-CD44 monoclonal antibody (IgG2a), were investigated on leukemia cells obtained from 31 patients with AML-M2, AML-M3, AML-M4 or AML-M5. When the AML cells were treated with HI44a, the percentage of nitroblue tetrazolium (NBT)+ cells was significantly increased. The expression of CD11b, CD14 and CD15 on treated AML cells was also increased compared to control AML cells. In addition, HI44a was found to induce apoptosis of leukemia cells, as evidenced by an annexin-V assay. The mean percentage of apoptotic cells in HI44a-treated AML cells was significantly increased compared to that in control AML cells. Moreover, the level of c-myc transcript expression on AML cells was found to be obviously decreased in all detected patients. These results indicate that HI44a effectively induces both differentiation and apoptosis of AML cells and suggest that this activity of the anti-CD44 antibody may be associated with its inhibitory effect on c-myc transcript expression.