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The development of the epidermal growth factor (EGF) receptor and transforming growth factor alpha (TGF alpha) receptors (p170 and p145) was investigated by immunohistochemical analysis in the tongue mucosa of rats which were given carcinogens of the aromatic amine (2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-nitrofluorene (NF) or N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) to induce oral squamous cell carcinoma (SCC). Changes in EGF-binding capacity (EBC) of the SCC-derived cell line RI-1 in relation to malignant transformation and tumorigenicity of rat tongue SCC cells in nude mice were also studied. The results were as follows: (1) The EGF receptor-immunoreactivity in the epithelial cell-layer of rat tongue, in particular the basal cell-layer, had a similar distribution to that of EGF-binding activity, as determined by EBC. (2) The pattern of immunoreactivity and EBC for the p170 and p145 receptors were not identical to each other, although in the basal cell-layer of the epithelium they appeared to be overlapped. (3) EBC and immunoreactivity of the two receptors decreased significantly at the early stage of carcinogenesis and increased at the later stage, with respect to the control. (4) The EBC and immunoreactivity of the receptors increased significantly when cells from carcinogen-treated tongue were transplanted into nude mice. (5) The changes of EBC and immunoreactivity were a little different among the three carcinogens. (6) The alteration in EBC and immunoreactivity of receptors was much more prominent in the long-term tumor-bearing group than in the group exposed for only 14 days to the carcinogen. These results indicate that

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