Previous studies on the influence of a rural/urban setting on the prevalence of cardiovascular disease risk factors in children have not sufficiently controlled for socioeconomic status, race, gender, and perhaps, may not have included a representative sample of rural and urban children. This study compared the cardiovascular disease risk factors and rate of obesity of children living in rural and urban settings. It also determined the magnitude of the effect of the rural/urban setting on cardiovascular disease risk factors and obesity when controlling for race, socioeconomic status, and gender. The subjects were 2,113 third- and fourth-grade children; 962 from an urban setting and 1,151 from a rural setting. Height, weight, skinfolds, resting blood pressure, and total cholesterol levels were measured. Aerobic power (pVO2max) was estimated from cycle ergometry. Physical activity and smoking history were obtained from a questionnaire. Clustering analyses using adjustment for sample error indicated that total cholesterol, blood pressure, smoking, and physical activity levels of rural and urban children were not different (P > 0.10); however, body mass index and sum of skinfolds was greater for rural youth (P < 0.004). Logistic regression indicated that rural children had a 54.7 percent increased risk of obesity (P = 0.0001). This study's results indicate that, in children, a rural setting is associated with obesity, but not with the major risk factors associated with cardiovascular disease.