Peptides corresponding to residues from Loops I and III of platelet-derived growth factor-BB (PDGF-BB) were examined for their potential to act as PDGF antagonists. We have identified two peptides which directly stimulated DNA synthesis in human dermal fibroblasts and a cyclic peptide which inhibited PDGF-induced DNA synthesis. The inhibitory action of cyclic PDGF-BB(73-81), on DNA synthesis was shown to be restricted to cells which express PDGF receptors. Also cyclic PDGF-BB(73-81) specifically competed for 125I-labelled PDGF-BB but not for 125I-labelled EGF binding to their respective cellular receptors. The cyclic peptide therefore provides a minimum structure to investigate PDGF/receptor interactions and our findings confirm the importance of the loop configuration of PDGF-BB(73-81) in the native molecule. The cyclic peptide may constitute a basis for developing more potent inhibitors of PDGF action.