Because southwestern Indians have relative genetic homogeneity and environmental isolation, this study compared the prevalence of gastric carcinoma, pernicious anemia (PA), gastric ulcer, and duodenal ulcer (DU) among patients at the Phoenix Indian Medical Center. During 17 years, there were 129 patients with these four diseases. In comparison with rates for the general population, southwestern Indians approximated the expected numbers with gastric carcinoma and PA, but had marked deficits for gastric ulcer and DU. All with gastric carcinoma, PA, or gastric ulcer were Indian, but 26% of the 19 with DU were non-Indian, although the non-Indian hospital admission rate was only 0.5%. Almost one-third of the 41 Indians with peptic ulcer had only partial Indian heritage, and 9 of those 13 had DU. Among full-blooded southwestern Indians, who comprised 90% of hospital admissions, 60 had gastric carcinoma; 18, PA; 22, gastric ulcer; and 3, DU. In contrast with reported Caucasian experience, gastric lesions of Indians were much more likely (2.7 : 1.0) to be malignant than benign, this probability being highest (8.4 : 1.0) for the Hohokam (Pima-Papago). Except for a vast predominance of blood group O, southwestern Indians had attributes generally compatible with the observed infrequency of peptic ulcer and moderate prevalence of gastric carcinoma and PA: rural reservation residence; lower socioeconomic level; noncompetitiveness; obesity; ABH salivary secretion; phenothiocarbamide taste sensitivity; high rates of diabetes mellitus and cholelithiasis; excessive drinking of alcohol; infrequent smoking of cigarettes; and low rates for chronic obstructive lung disease and coronary heart disease. Detailed gastric secretory studies and observation of future disease patterns in southwestern Indians may increase the understanding of these disorders.