Animal species of similar body mass vary widely in basal metabolic rate (BMR). A central problem of evolutionary physiology concerns the anatomical/physiological origin and functional significance of that variation. It has been hypothesized that such interspecific differences in wild animals evolved adaptively from differences in relative sizes of metabolically active organs. In order to minimize confounding phenotypic effects and maximize relevant genetic variation, we tested for intraspecific correlations between body‐mass‐corrected BMR and masses of four organs (heart, kidney, liver, and small intestine) among six inbred strains of mice. We found significant differences between strains in BMR and in masses of all four organs. Strains with exceptionally high (or low) BMR tended to have disproportionately large (or small) organs. The mass of each organ was correlated with the masses of each of the other three organs. Variation in organ masses accounted for 52% of the observed variation in BMR, of which 42% represented between‐strain variation, and 10% represented within‐strain variation. This conclusion is supported by published measurements of metabolic rates of tissue slices from the four organs. The correlation between BMR and intestine or heart mass arose exclusively from differences between strains, while the correlation between BMR and liver or kidney mass also appeared in comparing individual mice within the same strain. Thus, even though the masses of the four examined organs account for no more than 17% of total body mass, their high metabolic activities or correlated factors account for much of the variation in BMR among mice. We suggest that large masses of metabolically active organs are subject to natural selection through evolutionary trade‐offs. On the one hand, they make possible high‐energy budgets (advantageous under some conditions), but on the other hand they are energetically expensive to maintain.