Tumor promoting phorbol esters, 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol-12,13-dibutyrate (PDBu), significantly enhanced the growth of human gastric cancer cell line TMK-1, whilst activating protein kinase C. The time course of 125I-epidermal growth factor (EGF) binding to TMK-1 cells after TPA treatment showed a decrease in the number of EGF receptors on TMK-1 cells within 3 hr. Autophosphorylation of EGF receptor decreased in accordance with the decrease of EGF binding by TPA treatment. Scatchard plot analysis of TMK-1 cells after TPA treatment showed that high affinity EGF receptor disappeared at 3hr but the number of EGF receptors increased at 24 hr. These findings suggest that tumor promoting phorbol esters stimulate the cell growth through activation of protein kinase C and modification of EGF receptor of human gastric cancer cell line TMK-1.