Animals on islands often exhibit dramatic differences in morphology and behaviour compared with mainland individuals, a phenomenon known as the ‘island syndrome’. These differences are thought to be adaptations to island environments, but the extent to which they have a genetic basis or instead represent plastic responses to environmental extremes is often unknown. Here, we revisit a classic case of island syndrome in deer mice ( Peromyscus maniculatus ) from British Columbia. We first show that Saturna Island mice and those from neighbouring islands are approximately 35% (approx. 5 g) heavier than mainland mice and diverged approximately 10 000 years ago. We then establish laboratory colonies and find that Saturna Island mice are heavier both because they are longer and have disproportionately more lean mass. These trait differences are maintained in second-generation captive-born mice raised in a common environment. In addition, island–mainland hybrids reveal a maternal genetic effect on body weight. Using behavioural testing in the laboratory, we also find that wild-caught island mice are less aggressive than mainland mice; however, laboratory-raised mice born to these founders do not differ in aggression. Together, our results reveal that these mice have different responses to the environmental conditions on islands—a heritable change in a morphological trait and a plastic response in a behavioural trait.