The relation between total caloric intake, body weight, and tumorigenesis, as well as the independence of these effects from those of dietary fat, were evaluated using data from 82 published experiments involving several tumor sites in mice. Comparing experimental (calorie restricted) to control (ad libitum) groups showed that the former consumed 29% fewer calories (experimental groups consumed fewer calories than control groups in all but a few isocaloric experiments), 50% less total fat, 11% less protein, and weighed 25% less than control animals. Adult body weight was highly correlated to caloric intake in both males (r = 0.85) and females (r = 0.74), although this correlation decreased with increasing caloric intake. Cumulative tumor incidence was, on average, 42% lower in the restricted groups. Multivariate regression analyses revealed that, regardless of the level of dietary fat, tumor incidence increased with increasing caloric intake and body weight over a wide range of intakes, including moderate caloric restriction (i.e., 7-20%). These data indicate that total caloric intake is an important determinant of tumorigenesis in mice, and that body weight may be a more sensitive indicator for this effect than is caloric intake alone.