Bone follows the eponymous Bone cousins, who appear as white-skinned bone shaped cartoon humanoids: everyman Fone Bone, wealthy and self-serving Phoncible P. "Phoney" Bone, and simpleminded Smiley Bone. When Phoney mounts an ill-fated campaign for mayor, he is forced out of their hometown of Boneville, with Smiley and a reluctant Fone Bone following him.
