Piceatannol (3,4,3'5'-tetrahydroxy-trans-stilbene), a plant secondary natural product that had previously been identified as an antileukemic principle, has been shown to be an inhibitor of protein-tyrosine kinase activity. Piceatannol inhibits the purified thymocyte protein-tyrosine kinase, p40, by competing for the peptide or protein substrate binding site (Ki = 15 microM). Piceatannol also inhibits the activity of the p56lck protein-tyrosine kinase measured either in LSTRA cell membranes or in intact cells. In contrast, piceatannol does not inhibit the activity of the cAMP-dependent protein kinase.