In previous papers, we reported the effects of viral, chemical, and physical carcinogens on the tumor-producing capabilities of the nodule outgrowth line D1. The present paper describes the tumor-producing capabilities of a series of nodule outgrowth lines in BALB/c mice negative for mammary tumor virus (MTV) and in BALB/c f. C3H mice positive for MTV. Of 7 outgrowth lines tested for their responsiveness to MTV, 6 showed increased tumor-producing capabilities. The responsiveness of any outgrowth line to MTV was not correlated with its background tumor potential. Also described are the effects of MTV, nodule-inducing virus (NIV), 3-methylcholanthrene (MCA), and prolonged hormone stimulation, applied singly and combined, on the tumor-producing capabilities of nodule outgrowth line D2. Single application of prolonged hormone stimulation, MTV, or MCA increased the tumor-producing capabilities of line D2; however, NIV had no measurable effect. Combined applications of MTV and MCA, MTV and hormone stimulation, and MCA and hormone stimulation had additive effects. The D series of nodule outgrowth lines is a good system to study the effects of MTV's and chemical carcinogens, applied individually or combined. The present studies and the previously reported ones indicate that different outgrowth lines respond differently to various oncogenic agents and that the response of an outgrowth line to a combination of several carcinogens cannot be predicted by its response to a single application of the agents.