In mammals, insulin-like growth factor-1 (IGF-1) is positively correlated with adult body mass, in comparisons made within a given species. In mice, IGF-1 deficiency is associated with dwarfism, whereas IGF-1 overproduction in transgenic animals causes gigantism. Surprisingly, the opposite is true in an inter-species context. We collected published plasma total IGF-1 data for adults of 36 mammalian species and analyzed it with respect to body mass. In contrast to the intra-species observation, this analysis revealed a significant negative correlation of plasma IGF-1 with body mass. Interestingly, IGF-1 is negatively correlated with longevity, and suppression of IGF-1 signalling in worms, flies and mice increases lifespan. Smaller mouse strains, for example, tend to have lower plasma IGF-1 levels and to be longer-lived. However, when plasma total IGF-1 was analyzed relative to the maximum lifespans of the 36 species examined here, there was no statistically significant correlation. Low plasma IGF-1 levels in larger mammalian species may be physiologically significant, considering the roles of this hormone in metabolism, tissue regeneration, and cancer incidence.