To study the charge-selective properties of the glomerular filter in renal disease, we measured the fractional clearance, relative to creatinine clearance (ECC), of the amylase isoenzymes pancreatic amylase and salivary amylase, which have identical size but different charge. In 63 healthy subjects the mean (and SD) fractional excretion of pancreatic amylase, 4.07% (1.24%), was fourfold that of salivary amylase: 1.02% (0.54%). For 29 patients with renal disease and proteinuria, the mean fractional excretion of pancreatic amylase was significantly lower, 3.31% (1.94%), and that of salivary amylase significantly higher, 2.06% (1.41%), than in controls. In these patients, fractional excretions of both these isoenzymes were negatively correlated with urinary excretion of beta 2-microglobulin and ECC. Evidently, differences in clearances of pancreatic and salivary amylase are a consequence of differences in charge-related glomerular filtration. The relative increase of salivary amylase clearance in patients with renal disease and proteinuria is most probably caused by a loss of the charge-selective properties of the glomerular basement membrane.