Glomerular hyperfiltration is a characteristic feature of insulin-dependent diabetes. We examined the relative roles of renal size, as well as glycemic parameters (HbA1c, glycosylated albumin, plasma glucose) in addition to growth hormone, somatomedin C, beta-hydroxybutyrate, alanine, and glycerol in determining the glomerular filtration rate (GFR). Sixty-two insulin-dependent patients with normal urinary albumin excretion rates (AER less than 15 micrograms/min), who were less than 50 years of age, were included in the study. Data were subjected to multiple regression analysis with GFR as a dependent variable. Renal volume was the primary statistical determinant of hyperfiltration, but HbA1c also significantly correlated with GFR. No correlation was found with glycosylated albumin or blood glucose, but RPF correlated strongly with GFR, and borderline correlation was found between renal volume and HbA1c. Renal hyperfiltration, defined as a GFR greater than 150 ml/min, was found in approximately 50% of patients with HbA1c values greater than 9.5%. Other studies suggest that such patients have a much higher risk of developing clinically evident diabetic nephropathy over the ensuing years. Renal volume appears to be the major determinant of GFR, but long-term metabolic control, as evidenced by the level of HbA1c, also contributes, partly independent of renal volume. Short-term metabolic control, as evaluated by blood glucose and serum-fructosamine, did not correlate with GFR. We suggest that exact determination of GFR and renal volume should be included in long-term prospective controlled intervention trials in patients with insulin-dependent diabetes mellitus (IDDM).