Although physical inactivity and obesity are known risk factors for many vascular diseases, their relationships with CKD are poorly documented.We therefore analysed longitudinal data on a US cohort of 9035 adults aged 30-74 who participated in the second National Health and Nutrition Examination Survey (NHANES II) in 1976-80.At baseline, participants underwent a structured interview as well as physical and laboratory measurements.Incident cases of treated end-stage CKD through 1992 were identified by record linkage between NHANES II and the Medicare end-stage renal disease registry, and CKDrelated deaths from the NHANES II Mortality Study.Over 12-16 years, there were 188 cases of incident CKD (158 cases per 10 5 person-years): 44 cases of treated end-stage CKD and 144 with CKD listed as an underlying or contributing cause of death.After adjustment for age, gender, race, body-mass index (BMI) and smoking using a proportional hazards model, physical inactivity was significantly associated with a higher risk of CKD: relative risk (RR) of moderately vs very active persons, RR=1.2, 95% confidence interval [0.7-1.9], and of inactive vs very active, ].Compared to normal weight persons (18.5=BMI<25 kg/m 2 ), those with morbid obesity (BMI=35) were at higher risk for CKD: RR=2.3 [1.0-4.9];however, neither overweight (25=BMI<30) nor obese (30=BMI<35) individuals were at higher risk.The proportion of CKD risk attributable to obesity in the population was 6.5% and to physical inactivity, 17%.The relationship of morbid obesity to CKD was largely mediated by diabetes and hypertension; adjustment for these conditions substantially attenuated the .In contrast, physical inactivity was related to CKD, independent of these factors. Tese data identify physical inactivity and obesity as new risk factors for CKD.The growing prevalence of these two conditions in the population may contribute to the relentless increase of CKD incidence and may represent targets for primary prevention.