Genetic factors are involved in the development of diabetic nephropathy in type-1 diabetes. We are examining the association of the angiotensin-converting enzyme (ACE), insertion/deletion (I/D) polymorphism with the presence of diabetic nephropathy in type-1 diabetic patients. 52 type-1 diabetic patients with diabetic nephropathy (30 with either microalbuminuria or macroalbuminuria and 22 with end stage renal disease on dialysis) were compared with 10 type-1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years and 27 non-diabetic healthy subjects. We found that the D-allele frequency was higher in patients with nephropathy than in the healthy and normoalbuminuric controls. There was an association in the DD polymorphism of the ACE gene with patients with diabetic nephropathy and not with the control subjects. We conclude that the DD genotype of ACE gene polymorphism is associated with diabetic nephropathy in patients with type-1 diabetes mellitus.