Early Holocene bison mandibles (Bison antiquus) from Nebraska, ca. 8500 y ago, were examined with a variety of modern histotechnological procedures and staining techniques. A pathological, anatomical diagnosis of moderately severe, locally extensive, mandibular osteomyelitis with intralesional spherules morphologically consistent with fungal pathogens in the genus Coccidioides was made. The modern distribution of the organisms in North America is restricted to the arid Southwest. This implies either the fossil home range of the fungi was larger than it is today or fossil bison migrated between endemic and nonendemic foci during the early Holocene.