Pernicious anemia (PA), previously considered rare among American Indians, was diagnosed in 18 Indians during a 16-yr period at the Phoenix Indian Medical Center. These patients, from ten different tribes, did not vary significantly from all adult hospital admissions in proportionate sex, tribe, or blood group distribution. The current minimum prevalence of PA for southwestern Indians is 1:514 beyond 50 yr of age and 1:293 after 60 yr of age. Despite a marked predominance of blood group 0 (81%), the Indians developed PA as frequently as other ethnic groups in which PA is strongly associated with blood group A. Their clinical and hematologic manifestations were similar to those of whites with PA. Of the 13 subjects tested immunologically, 11 demonstrated parietal cell antibodies, and six had blocking antibodies to intrinsic factor. During follow-up none developed gastric carcinoma, although this tumor— the most frequent malignancy among southwestern Indians-is correlated with PA in whites. The findings establish that PA in full-blooded south-western Indians is not rare and is clinically and immunologically similar to PA in whites.