We studied kidney glomerular structure and function in two groups of type I (insulin-dependent) diabetic subjects with 14-16 yr (group 1, n = 16) and 24-26 yr (group 2, n = 13) duration of diabetes and compared them to a group of 18 nondiabetic subjects with similar age ranges. Within each diabetic group, subjects were selected for normal kidney function (urinary albumin excretion <40 mg/24 h, normal blood pressure, creatinine clearance >90 ml · min-1 · 1.73 m-2) or for nephropathy (urinary albumin excretion >200 mg/24 h). Morphometric analysis of glomeruli revealed a significantly larger mean glomerular volume in subjects with nephropathy (group 2). Mesangial volumes were significantly greater in the nephropathic than the normoalbuminuric diabetic subjects in each group, but filtration surface per glomerulus was constant among all subjects. The percentage of scleriosed glomeruli was also significantly increased in the nephropathic subjects compared with the subjects with normal kidney function, in whom sclerosed glomeruli did not exceed 8%. In addition, there was a significant correlation between percentage of globally sclerosed glomeruli and glomerular volume in group 2 (r(s) = .79, P < .01) but not group 1 (r(s) = -.20, NS) subjects. Thus, glomerular size or individual capacity for glomerular expansion may determine the rate of progression of the loss of kidney function in subjects destined to develope diabetic nephropathy.