Many agents have been known to induce the differentiation of HL-60 cells. However, only a small number of reports on the basophilic differentiation of this cell line are known. In this study we show that the exposure of HL-60 cells to chloroquine induces to differentiate into basophils. This chloroquine-induced change suggests that the increase in intracellular pH and the upregulation of p21 with subsequent downregulation of cdc2 kinase are triggers for basophilic differentiation of this cell line.