Preliminary investigation on the mechanism of the growth inhibition by recombinant epiregulin(EPI)of epidermal carcinoma cell A431 is reported. Northern blotting indicated that the mRNA level of cyclin dependent kinase(CDK)inhibitor, p21(WAF1/CIP1), was increased significantly after stimulation of the recombinant epiregulin protein. Luc reporter revealed that STAT1 could bind the promoter region of p21 in response to the EPI signal. Flow cytometry assay showed that the EPI-induced growth inhibition was not related to the apoptosis. The above results indicate that the EPI-induced cell growth inhibition might result from the STAT1-stimulated expression of p21, leading to the G1 arrest.