The renal hemodynamic effects of short-term protein loading and short term protein restriction were studied in patients with renal disease. Eleven patients adhered to a high protein diet (1.8 g/kg/day) and, subsequently, to a low protein diet (0.6 g/kg/day) for four weeks each. Renal hemodynamics were studied at the end of the respective dietary periods. Glomerular filtration rate (inulin clearance) did not change significantly (delta %: -1.5 +/- 5.4%; mean +/- s.e.m.), whereas endogenous creatinine clearance was lower on the low protein diet (delta %: -7.8 +/- 2.8%; p less than 0.02), suggesting an interference with the tubular secretion of creatinine. Effective renal plasma flow was significantly lower on the low protein diet (223.7 +/- 47.6 ml/min vs 282.1 +/- 67.1 ml/min; delta %: -15.4 +/- 4.9%; p less than 0.02). As a result, filtration fraction increased from 0.18 +/- 0.01 on the high protein diet to 0.22 +/- 0.02 on the low protein diet (p less than 0.01). The low protein diet caused a significant decrease in protein excretion from 4.0 +/- 0.9 g/24 h to 3.1 +/- 0.7 g/24 h (p less than 0.02). Our study demonstrates that renal hemodynamic responses to more sustained protein loading and protein restriction differ from the reported responses to acute protein loading. Different mechanisms may be involved. In this light it is doubtful if the renal hemodynamic response to acute protein loading can predict a beneficial effect of protein restriction.