Since renal hemodynamic disturbances are important in renal injury and are exacerbated by elevated plasma amino acid concentrations in insulin-dependent diabetes, we measured glomerular filtration rate (GFR) and renal plasma flow (RPF) after an overnight fast and during amino acid infusion in 12 patients with NIDDM and nine normal subjects. In the diabetic patients (plasma glucose 12.4 +/- 0.6 mmol/liter), the fasting GFR (113 +/- 6 vs. 98 +/- 7 ml/min.1.73 m2 in normal subjects, P = 0.056) and RPF (635 +/- 37 vs. 540 +/- 20 ml/min.1.73 m2 in normal subjects, P less than 0.05) were increased. After amino acid infusion, the increase in GFR (159 +/- 7 vs. 121 +/- 6 ml/min.1.73 m2 in normal subjects, P less than 0.05) and RPF (970 +/- 51 vs. 700 +/- 18 ml/min.1.73 m2 in normal subjects, P less than 0.05) were augmented. Insulin infusion for 36 hours did not change these responses. After three weeks of insulin therapy (plasma glucose 5.9 +/- 0.2 mmol/liter), the amino acid-stimulated GFR (143 +/- 5 ml/min.1.73 m2) and RPF (836 +/- 30 ml/min.1.73 m2) declined (P less than 0.05), while the fasting values remained unchanged. The right kidney volume was measured by ultrasonography and found to decrease after three weeks of insulin therapy from 188 +/- 12 to 165 +/- 9 ml/1.73 m2 (P less than 0.05). However, both values were greater than that in the normal subjects, 124 +/- 13 ml/1.73 m2 (P less than 0.01). Glomerular hyperfiltration and hyperperfusion became augmented during hyperaminoacidemia in our NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)