The effect of epidermal growth factor (EGF) on the biological behaviour of human tumours in vivo is still controversial. We investigated the effect of EGF on the growth of an EGF receptor-hyperproducing human epidermoid carcinoma, A431 tumour, and on a human small-cell lung carcinoma, H69 tumour, without detectable EGF receptor by using sialoadenectomised (sialex) mice as an endogenous EGF-suppressed animal model. The plasma EGF concentration in the sialex athymic mice was significantly lower than that in the sham-operated mice (P < 0.05). After exogenous EGF replacement with an implanted minipump, the plasma EGF concentration was significantly increased in both groups (P < 0.05). There was no significant difference between the body weight growth curves of sialex and sham-operated mice with and without EGF treatment. The tumour weight of A431, both estimated and measured in sialex mice, was significantly lower than that in sham-operated control mice (P < 0.05), and the growth of A431 tumour was significantly increased by exogenous EGF treatment (P < 0.05). Mitotic activity of these tumours detected by immunohistochemical staining for incorporated bromodeoxyuridine indicated a mitosis-stimulatory effect of endogenous and exogenous EGF on A431 tumours. In contrast to these findings on A431 tumours, a growth-stimulatory effect of endogenous and exogenous EGF was not observed in the H69 tumour. These results suggest a growth-promoting effect of physiological levels of endogenous EGF on EGF receptor-hyperproducing human tumours in vivo.