OBJECTIVE The Pima Indians of Arizona have the highest reported prevalences of obesity and non-insulin-dependent diabetes mellitus (NIDDM). In parallel with abrupt changes in lifestyle, these prevalences in Arizona Pimas have increased to epidemic proportions during the past decades. To assess the possible impact of the environment on the prevalences of obesity and NIDDM, data were collected on members of a population of Pima ancestry (separation 700–1,000 years ago) living in a remote mountainous location in northwestern Mexico, with a lifestyle contrasting markedly with that in Arizona. RESEARCH DESIGN AND METHODS Pima heritage was established by history and by use of Pima language. Measurements of weight, height, body fat (bio-impedance), blood pressure, plasma levels of glucose, cholesterol, and HbA1c were obtained in 19 women (36 ±13 years of age) and 16 men (48 ±14 years of age) and compared with sex-, age- and diabetes status-matched Pimas living in Arizona (10 Arizona Pimas for each Mexican Pima). RESULTS Mexican Pimas were lighter (64.2 ± 13.9 vs. 90.2 ± 21.1 kg, P < 0.0001; means ± SD) and shorter (160 ± 8 vs. 164 ± 8 cm, P < 0.01) with lower body mass indexes (24.9 ± 4.0 vs. 33.4 ± 7.5 kg/m2, P < 0.0001) and lower plasma total cholesterol levels (146 ± 30 vs. 174 ± 31 mg/dl, P < 0.0001) than Arizona Pimas. Only two women (11%) and one man (6%) had NIDDM, contrasting with the expected prevalences of 37 and 54% in female and male Arizona Pimas, respectively. CONCLUSIONS This preliminary investigation shows that obesity, and perhaps NIDDM, is less prevalent among people of Pima heritage living a “traditional” lifestyle than among Pimas living in an “affluent” environment. These findings suggest that, despite a similar potential genetic predisposition to these conditions, a traditional lifestyle, characterized by a diet including less animal fat and more complex carbohydrates and by greater energy expenditure in physical labor, may protect against the development of cardiovascular disease risk factors, obesity, and NIDDM.