Despite considerable clinical experience with proteinuria, its prognostic meaning in the ambulatory general population is poorly documented. From a 16-year study of 5209 men and women in the Framingham cohort it is evident that proteinuria, even in casual urine specimens, carries substantial risk with the mortality rate increased threefold. Proteinuria was three times as common in hypertensive persons and also occurred to excess in diabetic patients and in persons with cardiac enlargement. In the absence of these factors, proteinuria was so uncommon that its risk could not be accurately assessed. Among persons with these associated risk factors, those with proteinuria have higher death rates than those without proteinuria. In men, overall mortality and cardiovascular mortality rates remained significantly increased even when other contributors to risk were taken into account. Proteinuria in the ambulatory general population is not a benign condition and carries a serious prognosis. It appears to reflect widespread vascular damage.