BACKGROUND: Smoking has been associated with the prevalence, development, and progression of kidney disease. The effect of smoking on kidney function in the healthy population is unclear. We examined the relationship between smoking and indicators of kidney damage in a healthy population without impaired fasting glucose levels, impaired glucose tolerance, diabetes mellitus, or hypertension. METHODS: This is a randomly selected, population-based, cross-sectional study of 11,247 Australian adults. Smoking status was determined by questionnaire. Subjects were tested for indicators of kidney damage: renal impairment by Cockcroft-Gault-estimated glomerular filtration rate less than 60 mL/min/1.73 m2 and proteinuria by urine protein-creatinine ratio of 0.20 mg/mg or greater. RESULTS: After adjusting for potential confounding factors, smoking was significantly associated with renal impairment in men with an odds ratio of 3.59, but not in women. Smoking was significantly associated with proteinuria in subjects with high-normal systolic blood pressure, with odds ratios ranging from 3.64 at 131.5 mm Hg to 5.76 at 139.5 mm Hg, and in subjects with high-normal 2-hour glucose levels, with odds ratios ranging from 1.76 at 7.0 mmol/L to 10.84 at 7.7 mmol/L. Lifetime exposure, but not current level of smoking, correlated with lower estimated glomerular filtration rate and greater urine protein-creatinine ratio. CONCLUSION: Smoking is associated with renal impairment and proteinuria in a population without hypertension or abnormal glucose metabolism. A dose-response relationship was found between cumulative amount of smoking and indicators of kidney damage. In conjunction with other studies and plausible biological mechanisms, this study suggests that smoking may cause kidney damage, even in a healthy population.