The Insulin Receptor (IR) is a potential oncogene for mammary epithelial cells since its content is increased in most human breast cancer specimens, and both ligand-dependent malignant transformation and ligand-dependent enhanced growth occurs in cultured breast cells overexpressing the IR. To better understand whether the IR plays a role in mammary carcinogenesis which is independent of other initiation factors, we measured IR content in transgenic mouse models of breast cancer induced by 3 known oncogenes (Wnt-1, Neu, and Ret). Insulin receptor content was measured by a specific radioimmunoassay. In normal mammary gland tissues IR content was 14.6 +/- 1.4 ng/mg of protein (mean +/- SEM, n = 6). In the 3 cancers IR content was elevated (Neu = 36.1 +/- 4.6, n = 8, p < 0.002; Wnt-1 = 38.3 +/- 2.6, n = 13, p < 0.001; and Ret = 53.6 +/- 7.1, n = 7, p < 0.001). These data indicate that IR overexpression, in addition to being a potential oncogene, is increased in mouse tumors initiated by other oncogenes, and therefore may also play a supportive role in the growth of breast cancers.