A major change in mammary tumor incidence (MTI) and latency has occurred in the C3H/HeJ mouse substrain maintained at The Jackson Laboratory. The average time required for 50% of the C3H/HeJ mice to develop a mammary tumor changed from 40 weeks of age to the current 61 weeks of age. This 61-week median MTI in the C3H/HeJ substrain is significantly different from the less than 40-week median MTI seen in other C3H substrains infected with an exogenous milk-transmitted murine mammary tumor virus (MuMTV). The median MTI of over 80 weeks in MuMTV-negative C3H substrains also is significantly longer than that seen in C3H/HeJ mice. Although the median MTI for the C3H/HeJ substrain has changed significantly, the continued presence of an exogenous MuMTV in C3H/HeJ mice was confirmed by the presence of high levels of gp52 antigen in the milk of lactating females. Presence of an exogenous MuMTV in C3H/HeJ female mice also was confirmed by their ability to pass their exogenous MuMTV(HeJ) via their milk to exogenous MuMTV-negative BALB/cByJ, C3H, or C3H hybrid mice. These foster-nursed mice exhibited the reduced tumor frequency and the increased median MTI seen in their C3H/HeJ foster mothers. The change in tumor incidence and latency in the C3H/HeJ substrain is not due to the loss of the exogenous MuMTV but to the occurrence of an attenuated MuMTV. Selection of this attenuated MuMTV may be related to the presence of the Lps mutation that occurred during the same time period that the MTI changed in the C3H/HeJ substrain.