The southeastern region of the United States has long been considered to have higher rates of nephrolithiasis than other regions. Previous reports examined hospital discharge rates for nephrolithiasis rather than stone incidence rates and did not evaluate potential confounding variables. We studied prospectively the regional rates of incident stone formation within the United States in a cohort of 45,289 men 40 to 75 years old in 1986 who had no history of kidney stones. Dietary intake was measured by a semiquantitative food frequency questionnaire. During 6 years of followup 753 incident cases of kidney stones were documented. We also examined regional prevalence among 4,082 men who had a history of nephrolithiasis at the start of the study. There were no significant differences in age-adjusted incidence rates between the Southeast and other regions. Controlling for other risk factors, including age and relevant nutrients, did not alter the results. The prevalence of stone disease was significantly greater in the Southeast. Using the Southeast as the comparison region, a decreased risk of having a history of kidney stones was found, ranging from 13% (95% confidence interval 4 to 21%) lower in the Mid-Atlantic region to 31% (95% confidence interval 21 to 40%) lower in the Northwest. The prevalence in all other regions combined compared to the Southeast was also lower (odds ratio 0.82, 95% confidence interval 0.76 to 0.89). Therefore, individuals in the Southeast appear to have an overall greater risk of kidney stones. However, the magnitude of this effect is modest compared with previous estimates.