Little is known about the magnitude and nature of the combined effect of chronic kidney disease (CKD) and smoking on cardiovascular diseases. We studied this in a Japanese population using a pooled analysis of 15,468 men and 19,154 women aged 40-89 years enrolled in 8 cohort studies. The risk of mortality from all-causes and cardiovascular disease was compared in 6 gender-specific categories of baseline CKD status (non-CKD or CKD) and smoking habits (lifelong never smoked, former smokers, or currently smoking). CKD was defined as a decreased level of estimated glomerular filtration rate (under 60 ml/min per 1.73 m(2)) and/or dipstick proteinuria. Hazard ratios were estimated for each category, relative to never smokers without CKD. During the follow-up period (mean 14.8 years), there were 6771 deaths, 1975 of which were due to cardiovascular diseases. In both men and women, current or former smokers with CKD had the first or second highest crude mortality rates from all-cause and cardiovascular diseases among the 6 categories. After adjustment for age and other major cardiovascular risk factors, the hazard ratios in male and female current smokers with CKD were 2.26 (95% confidence interval, 1.95-2.63) and 1.78 (1.36-2.32) for all-causes, and 2.66 (2.04-3.47) and 1.71 (1.10-2.67) for cardiovascular diseases, respectively. Thus, coexistence of CKD and smoking may markedly increase the risk of all-cause and cardiovascular mortality.