The chemotactic activities of three different isoforms of platelet-derived growth factor (PDGF) on fibroblasts, monocytes, and granulocytes of human origin were investigated. PDGF-AB and PDGF-BB induced strong, dose-dependent responses in both fibroblasts and monocytes, whereas PDGF-AA did not stimulate chemotaxis of these cell types. Instead, PDGF-AA inhibited the chemotactic activity of PDGF-AB and PDGF-BB on fibroblasts and monocytes. However, PDGF-AA was not able to block monocyte chemotaxis induced by FMLP. In contrast, in granulocytes, dose-dependent chemotactic responses were obtained with all three isoforms of PDGF. All isoforms gave maximal responses at concentrations between 5 and 20 ng/ml. At higher concentrations the migration was reduced. Reduction and alkylation of the PDGF molecule, which leads to loss of the mitogenic activity, also caused a loss of the chemotactic activities for all three cell types. The data suggest that the various isoforms of PDGF stimulate and inhibit chemotaxis in an isoform- and cell type-specific manner.