Runcorn, North West England, has been a site of industrial activity for over 100 years. Preliminary investigations have revealed excess risk of renal mortality in the population living closest to several sources of pollution. Exposure to airborne mercury has been highlighted as a possible cause, although there is also concomitant exposure to solvents and other heavy metals in this population. The authors used validated air dispersion modeling to identify mercury-exposed populations. Standardized mortality ratios for kidney disease were computed using the North West government region as the reference. There was a significant exposure-response relation between modeled estimates of mercury exposure and risk of kidney disease mortality (test for trend: p = 0.02 for men and p = 0.03 for women), and this relation was more pronounced for estimated historical exposure (test for trend: p = 0.01 for men and p < 0.001 for women). These findings suggest that exposure to mercury is a possible cause of the excess kidney disease mortality in this population, indicating that there might still be a health legacy of the historically high levels of industrial activity in the Runcorn area.