We propose to conduct a prospective study of risk factors for incident and recurrent calcium nephrolithiasis among female and male participants of two large ongoing cohort studies: the Nurses' Health Study I(121,000 participants) and the Health Professionals Follow-up Study (52,000,). The primary objective will be to identify preventable causes of nephrolithiasis which occurs in 12% of the US population and is an important cause of morbidity. There are no prospective studies relating risk factors to incident or recurrent stone formation. Retrospective studies and our preliminary work suggest several dietary hypotheses that will be a major focus of this investigation. Specifically, we will address the hypotheses that diets high in calcium, animal protein, sodium and sucrose increase the risk of nephrolithiasis whereas diets high in potassium lower the risk. Stone formation will also be examined in relation to other factors associated with risk including gender and family history. Twenty-four hour urine samples (approximately 1200 total) will be collected from a sample of cases and controls to examine the relation between risk factors and nephrolithiasis stratified by urinary composition of relevant factors. Information on dietary and other exposure variables is collected by biennial mailed questionnaire. Dietary variables are measured by a semiquantitative food frequency questionnaire developed and refined by our group over the past 15 years. Information on the occurrence of kidney stones is also collected by the mailed questionnaires and confirmed by a supplementary questionnaire and a review of medical records. During the five years of follow-up, we expect over 760 incident and 270 recurrent stones in women and over 1100 incident and 420 recurrent stones in men. For incident nephrolithiasis, this will provide a power of 0.99 to detect a relative risk of 1.6 for extreme quintiles of dietary factors. For a first recurrence of nephrolithiasis, the power will be 0.78 in women and 0.95 in men for the same comparison. The magnitude of this common, painful and costly medical problem and the lack of knowledge regarding its etiologic risk factors makes this an important public health issue. We believe the proposed study, which is highly cost effective since it makes use of existing cohorts, will provide data on potentially modifiable risk factors which could have direct clinical application in decreasing the risk of nephrolithiasis.