The insertion/deletion (I/D) polymorphism of the angiotensin-converting-enzyme (ACE) gene has been reported to be associated with diabetic nephropathy in IDDM. We studied the relationship between this polymorphism and diabetic nephropathy in 210 IDDM patients. Their DNA was analyzed by polymerase chain reaction to type for the presence (I) or absence (D) of the 287 bp fragment in intron 16 of the ACE gene. The relative frequency of the different genotypes was 33.8% (DD), 43.8% (ID), and 22.4% (II). There were no significant differences between the genotypes in age, body-mass-index, blood pressure, plasma total cholesterol and triglycerides. The prevalence of microalbuminuria or nephropathy was 23.9% in the DD, 16.3% in the ID, and 17% in the II genotypes. The higher percentage of microalbuminuria or nephropathy in the DD genotypes was due to an increasing frequency of DD genotypes in the IDDM patients with long diabetes duration. After matching for diabetic retinopathy, gender, and diabetes duration, there was no association between the ACEI/D polymorphism and diabetic nephropathy. In conclusion, these results suggest that the ACE DD genotype cannot be regarded as a risk factor for diabetic nephropathy, but may even be associated with diabetes duration and thus longevity in IDDM patients.