Delphinidin has been reported to inhibit EGFR signalling. To determine whether other receptor tyrosine kinases (RTKs) are also influenced by delphinidin, we examined its ability to inhibit the kinase activity of EGFR, ErbB2, VEGFR-2, VEGFR-3 and IGF1R in a cell-free test system. We found that delphinidin strongly inhibited the protein tyrosine kinase activity of all tested RTKs at low micromolar concentrations. In A431 and PAE cells, ligand-induced phosphorylation of the receptors was also potently suppressed, with a preference for the suppression of the activity of ErbB3 (IC(50) approximately 100 nM) and VEGFR-3 (IC(50) < 50 microM). Thus the inhibition of RTKs by delphinidin is not limited to cell-free assays but is also of relevance in the cellular context. The results indicate that delphinidin acts as a broad-spectrum inhibitor of RTKs. Given the crucial role of the receptors in tumour growth and metastasis, we conclude that delphinidin has the potential to act directly against tumour cells as well as to interfere with key tumour-host interactions, although the suitability of delphinidin as a drug in cancer management may be compromised by its limited stability. Nevertheless, delphinidin may represent a novel lead compound for the development of chemopreventative and chemotherapeutic intervention strategies.