Although there is a high prevalence of overweight among Navajo children and adolescents, other risk factors for chronic disease in this population have received little attention. We therefore examined the distribution and interrelationships of overweight, cigarette smoking, blood pressure and plasma levels of lipids and glucose among 160 Navajo 12- to 19-y-olds. In agreement with previous reports, participants were approximately 2 kg/m2 heavier than adolescents in the general U.S. population, and the prevalence of overweight (> 85th percentile) was 35-40%. Levels of total cholesterol and blood pressure were similar to those in the general U.S. population, but Navajo adolescents had a 5-10 mg/dL lower median level of HDL cholesterol, and a 30 mg/dL higher median triglyceride level. Eight percent of the adolescents examined had either impaired glucose tolerance or diabetes mellitus as assessed through an oral glucose tolerance test (n = 10) or self-report (n = 1). Relative weight (kg/m2) was associated with adverse levels of lipids, lipoproteins and glucose, with overweight adolescents having a fivefold greater risk for elevated triglyceride levels than other adolescents. Tobacco use was fairly prevalent among boys (24% cigarettes, 23% smokeless tobacco), but not girls (9% cigarettes, 3% smokeless tobacco). Because of its associations with other risk factors and with various chronic diseases in later life, it may be beneficial to focus on the primary prevention of obesity among Navajo children and adolescents.