were observed in 62% of the untreated C3HIStMTV glands at 8 months of age. Therefore, MMTV(S) was present and active in the mammary gland during the experimental period but had no enhancing influence on the sensitivity of the gland t o carcinogenesis by DMBA. Tumors appearing in DMBA-treated C3HIStWi virgin females were also tested for M M N gp52 and p27 antigens to determine the presence of endogenous MMTV gene activity. Only occasional C3HIStWi tumors were positive and in most of these, p27, but not gp52 was detected, suggesting non-coordinate expression of these endogenous M M N gene products. Both alveolar (HAN) and ductal hyperplasia (DH) were found in DMBAtreated C3HIStMN glands, whereas only D H were found in DMBA-treated C3HIStWi mice. Nevertheless, the DMBA-induced C3H/StMTV tumor histopathology was remarkably indistinguishable from that in tumors produced by DMBA in C3HIStWi mice, implying that in both groups, tumors arose primarily from the chemically-induced mammary dysplasias. These data taken together appear to support the conclusion that DMBA and MMTV follow separate pathways to the induction of cancer in the mouse mammary gland.The C3H/StWi mouse subline spontaneously lost its milk-borne exogenous mouse mammary tumor virus [MMTV(S)] in 1958 and became a low mammary cancer strain (Smith, 1966). The subline remains highly susceptible to the reintroduction of MMTV(S) and can be readily converted to a high incidence mammary cancer subline. However, the mice can neither express their endogenous, genetically-transmitted mammary tumor virus [MMTV(L)] as virions nor are they susceptible to infection by these virions when introduced from without. Previous studies in our laboratories have shown that C3H/StWi virgin females are susceptible to chemical induction of mammary cancer with DMBA (46 %), while remaining relatively unsusceptible to the appearance of mammary preneoplasia and neoplasia even in the presence of chronic, exogenous steroid stimulation of the mammary glands (Smith et al., 1978). Chemical induction of mammary neoplasia in C3WStWi virgin females was accompanied by the appearance of mammary ductal hyperplasias (73 %) and the conspicuous absence of the mammary alveolar hyperplasia commonly associated with MMTV carcinogenesis. In addition, no increase in the steady-state levels of endogenous MMTV RNA transcription was detected in these chemically-induced mammary tumors nor was there evidence of virion production by electron microscopy. Although an increase in endogenous MMTV gene transcription was not measurable, a qualitative change in endogenous MMTV gene expression could not be ruled out and endogenous MMTV gene activity was not evaluated by immunological techniques. Thus, while quantitative estimations of MMTV gene transcription suggested a dichotomy between the expression of endogenous MMTV DNA sequences and DMBA-induced mammary carcinogenesis, qualitative changes in gene expression were not tested. Our present approach has been to test C3WStWi normal mammary tissues and spontaneous or chem...