A series of 22 flavanoids and related compounds were tested for their ability to inhibit the activity of a protein-tyrosine kinase purified from bovine thymocytes (p40). Flavones or flavanols with hydroxyl groups at C-5 and C-7 or with three hydroxyl groups on the phenyl ring were potent inhibitors of p40. The replacement of hydroxyl groups with methoxyl groups led to a substantial loss of inhibitory activity. The presence of methoxyl or rhamnosyl substituents at C-3 also abolished inhibitory activity. Kinetic analyses indicated that the flavone apigenin  was a competitive inhibitor of p40 with respect to ATP. Flavanones and isoflavones were relatively inactive as protein-tyrosine kinase inhibitors. The isoflavone genistein , which has been reported as a potent inhibitor of both pp60(v=src) and the epidermal growth factor receptor, was not an inhibitor of p40.