Transgenic mice have been used to demonstrate that the myc transgene, fused to the murine mammary tumor virus LTR promoter, leads to development of mammary tumors. To study the role of the Myc protein in these tumors, a sensitive immunohistochemical method was used to compare the Myc protein expression in mammary tumors and normal mammary gland from two independent MTV/myc transgenic lines. The highest levels of staining for Myc were found in the epithelial cell nuclei of mammary tumors and foci of mammary hyperplasia. Normal transgenic epithelium had only scattered foci of low intensity staining nuclei. The nuclei of transgenic mesenchyme and of non-transgenic mammary glands of control FVB mice did not contain detectable antigen. This work supports the hypothesis that the Myc protein can play a role in mammary tumorigenesis and suggests a correlation between high levels of Myc and the development of histopathology.