Glomerular hyperfiltration and microalbuminuria are both regarded as risk factors for the development of diabetic nephropathy in insulin-dependent diabetic patients. Information on glomerular hyperfiltration is scarce in microalbuminuric non-insulin-dependent diabetic (NIDDM) patients. Therefore, we performed a cross-sectional study of glomerular filtration rate (single i.v. bolus injection of 51Cr-EDTA, plasma clearance for 4 h) in 158 microalbuminuric NIDDM patients compared to 39 normoalbuminuric NIDDM patients and 20 non-diabetic control subjects. The groups were well-matched with regard to sex, age and body mass index. The uncorrected (ml/min) and the adjusted (ml. min-1. 1.73 m-2) glomerular filtration rate were both clearly elevated in the microalbuminuric patients: 139 +/- 29 and 117 +/- 24 as compared to 115 +/- 19 and 99 +/- 15; 111 +/- 23 and 98 +/- 21 in normoalbuminuric NIDDM patients and control subjects, respectively (p < 0.001). The glomerular filtration rate (ml. min-1. 1.73 m-2) in NIDDM patients who had never received antihypertensive treatment was also clearly elevated in the microalbuminuric patients (n = 96): 119 +/- 22 as compared to 100 +/- 14 and 98 +/- 21 in normoalbuminuric NIDDM patients (n = 27) and control subjects (n = 20), respectively (p < 0.001). Glomerular hyperfiltration (elevation above mean glomerular filtration rate plus 2 SD in normoalbuminuric NIDDM patients) was demonstrated in 37 (95% confidence interval 30-45)% of the microalbuminuric patients. Multiple regression analysis revealed that HbA1c, 24-h urinary sodium excretion, age and known duration of diabetes were correlated with glomerular filtration rate in microalbuminuric NIDDM patients (r2 = 0.21, p < 0.01). Our cross-sectional study indicates that NIDDM patients at high risk of developing diabetic nephropathy are also characterized by an additional putative risk factor for progression, glomerular hyperfiltration.