The insulin/insulin-like growth factor signalling pathway has been hypothesized as a major determinant of life-history profiles that vary adaptively in natural populations. In Drosophila melanogaster, multiple components of this pathway vary predictably with latitude; this includes foxo, a conserved gene that regulates insulin signalling and has pleiotropic effects on a variety of fitness-associated traits. We hypothesized that allelic variation at foxo contributes to genetic variance for size-related traits that vary adaptively with latitude. We first examined patterns of variation among natural populations along a latitudinal transect in the eastern United States and show that thorax length, wing area, wing loading, and starvation tolerance exhibit significant latitudinal clines for both males and females but that development time does not vary predictably with latitude. We then generated recombinant outbred populations and show that naturally occurring allelic variation at foxo, which exhibits stronger clinality than expected, is associated with the same traits that vary with latitude in the natural populations. Our results suggest that allelic variation at foxo contributes to adaptive patterns of life-history variation in natural populations of this genetic model.