Glomerular charge selectivity was assessed using the ratio of the clearance of pancreatic isoamylase to the clearance of the more anionic salivary isoamylase (CPAm/CSAm) in 12 normal subjects and 50 patients with Type 1 diabetes: 13 with normal albumin excretion and short duration of diabetes (< 5 years), 15 with normal albumin excretion and long duration of diabetes (> 15 years), 13 with microalbuminuria, and 9 with clinical nephropathy. None had serum creatinine > 200 mumol l-1. There were no significant differences in CPAm/CSAm between the normal subjects and the two groups of normoalbuminuric patients with Type 1 diabetes. CPAm/CSAm was significantly lower in diabetic patients with microalbuminuria or clinical nephropathy than in normoalbuminuric patients with Type 1 diabetes. When the 37 patients with normoalbuminuria and long-standing diabetes, microalbuminuria, and nephropathy were considered together, there was a significant negative correlation between CPAm/CSAm and albumin excretion rate (rs = 0.71, p < 0.001). Progressive impairment of glomerular charge selectivity at the molecular size of amylase (molecular mass 56 kDa) accompanies increasing albuminuria in Type 1 diabetes.