Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.