The effect of epidermal growth factor on the radiation response of two human squamous carcinoma cell lines, A431 (from vulva) and SiHa (from cervix), was examined. In both lines, cells in S phase were more radioresistant than cells in other cell cycle phases. Epidermal growth factor present after irradiation enhanced the radiation response of A431 cells in different cell cycle phases, whereas no effect was seen for SiHa cells. The enhancement was maximum with 10 ng/ml epidermal growth factor and was associated mainly with a reduction in the shoulder region of the cell survival curve. The ratio between the n values of the control and epidermal growth factor treated total cell population, G1, S, and G2M cells is 2.2, 4.1, 1.7, and 2.2, respectively. Epidermal growth factor reduced plating efficiency by about 50% for A431 cells in different cell cycle phases whereas a slight increase in plating efficiency was seen for SiHa cells. The present results indicate that epidermal growth factor related radiosensitization is dependent on both cell line and cell cycle.