Porotic hyperostosis was observed in 34 percent of 539 crania excavated from sites in Arizona and New Mexico. Common causes of this cranial pathology in the Old World (thalassemia, sickle cell anemia, and malaria) do not explain its occurrence in the American Southwest, as malaria and hemoglobinopathies are not known to have existed in the New World prior to European contact. Iron deficiency anemia which may also be associated with porotic hyperostosis occurs on a mass level only with hookworm infestation or nutritionally-related iron deficiency. Since hookworm infestation is rare in the American southwest and has not been reported in prehistoric southwestern American Indians, the hypothesis of nutritional anemia was examined. In canyon bottom sites where the diet was heavily dependent on maize, which is low in iron and also contains an inhibitor of iron absorption, significantly more crania had porotic hyperostosis than in sage plain sites, where the diet included ample animal protein rich in easily absorbable iron (p < .001). Furthermore, canyon bottom children, who were more susceptible to iron deficiency anemia, had a higher incidence of porotic hyperostosis lesions than adults (p < .0001).