Glomerular hyperfiltration is one of the factors held responsible for the development of diabetic nephropathy. A supranormal glomerular filtration rate (GFR) can be found in diabetic patients even when they are well controlled. Infusion of low-dose dopamine demonstrates that glomerular hyperfiltration in well-controlled insulin-dependent diabetic patients is not based on a predominant vasodilatation of the efferent arteriole. In the present study this is confirmed, since the dopamine-induced rise in GFR of control subjects (13.5% +/- 2.2) did not differ from that of patients with insulin-dependent diabetes mellitus (10.8% +/- 2.1). In animal studies it has been demonstrated that the increased GFR in diabetes mellitus is caused by a predominant decrease in resistance of the afferent arteriole. Protein loading and infusion of amino acids also increase GFR by dilatation of the afferent arteriole. Thus, protein loading or amino acid infusion may be used to test the existence of afferent vasodilatation. The present study investigates the effect of amino acid infusion on GFR of control subjects and insulin-dependent diabetic subjects. The amino acid-induced rise in GFR tended to be lower in the diabetic patients (6.9% +/- 2.8) compared with controls (13.2% +/- 2.7). Percentage amino acid-induced change in GFR appeared to decline with increasing baseline GFR in the diabetic subjects (r = -0.83; P less than 0.001). In controls, no such relationship was established (r = -0.22; n.s.). Our results suggest the existence of afferent vasodilatation in diabetic patients with a high GFR. The cause of this vasodilatation warrants further study.