Platelet‐derived growth factor (PDGF) is one of the most important polypeptide growth factors in human serum. It is composed of two polypeptide chains linked by disulfide bonds. The B‐chain is encoded by the c‐sis proto‐oncogene, which is expressed in several malignant and non‐malignant cells including K562 cells differentiating towards megakaryoblasts. Expression of the A‐chain has been reported to occur in human solid tumor cell lines independently of c‐sis expression. We report here the non‐coordinate expression of the A‐ and B‐chains in human leukemia cell lines. The PDGF‐A and B‐chain (c‐sis) RNA expression as well as secretion of PDGF polypeptides are induced in the K562 cell line upon induction of megakaryoblastic differentiation with 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA) whereas erythroid differentiation induced with sodium butyrate is accompanied by c‐sis expression only. Simultaneously with megakaryoblastic differentiation the RNA level for another platelet protein, the transforming growth factor‐beta was also increased, but in a complex manner. The promyelocytic leukemia cell line HL‐60 does not express PDGF‐A RNA, whereas the promonocytic cell line U937 does. Preferential induction of the A‐chain RNA is obtained in both cell lines after treatment with TPA which causes monocytic differentiation. PDGF‐A expression in HL‐60 cells is also observed after treatment with the tumor necrosis factor‐alpha but granulocytic differentiation of HL‐60 cells induced with dimethyl sulfoxide or the granulocyte colony‐stimulating factor is not associated with PDGF gene expression.