Antibody levels to mouse mammary tumor virus (MuMTV) in sera of C3H/Bi, C57BL/6 and AKR mice were assayed by an enzyme-linked immunosorbent assay (ELISA). It was found that antibody levels to MuMTV were highest in sera of C3H/Bi females which have a high incidence of breast cancer and low in male C3H/Bi and female C3H/Bi foster-nursed on C57BL/6 females. Sera of C57BL/6 and AKR mice showed very low or undetectable levels of antibody to MuMTV. Reduction of caloric intake sufficient to inhibit mammary tumor formation strikingly inhibited formation of antibody against MuMTV. The lowest levels of antibody were observed in sera of mice fed 10 cal/day of a defined diet. Significantly higher levels developed in the sera of mice fed 16 cal/day of the same defined diet. The highest antibody levels against MuMTV, however, were seen in sera of mice fed lab chow ad libitum but no correlation was evident between levels of antibody and tumor size. These studies indicate that dietary caloric restriction has a profound influence on the development of both mammary adenocarcinoma and antibody responses to MuMTV.