Thickening of the basement membrane and other structural alterations of the vascular walls occur frequently in patients with diabetes. The vascular response to atrial natriuretic peptide (ANP) is also altered in these patients. Abnormal vascular response in diabetes may be due to alteration of vascular physicochemical properties induced by accumulation of components of vascular basement membrane. The aim of this study was to evaluate the relationship between circulating levels of the 7 S domain of type IV collagen (7 S-collagen), and ANP in normotensive type 2 diabetic patients with or without retinopathy. Forty-one normotensive type 2 diabetic patients (n = 19 with and n = 22 without retinopathy) and 18 age-matched control subjects participated in the study. Serum 7 S-collagen and plasma ANP levels were measured by radioimmunoassays. Serum 7 S-collagen (4.4 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01) levels and plasma ANP (20.8 +/- 1.0 vs 15.5 +/- 1.0 pg/ml; p < 0.01) were significantly higher in diabetic patients than in normal subjects. Serum 7 S-collagen increased significantly in diabetic patients without retinopathy compared with normal subjects (4.1 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01). Diabetic patients with retinopathy showed significantly higher circulating concentrations of 7 S-collagen (4.6 +/- 0.1 vs 4.1 +/- 0.1 ng/ml; p < 0.01) and ANP (22.9 +/- 1.4 vs 18.9 +/- 1.3 pg/ml; p < 0.05) than those without retinopathy. There was a significant and positive correlation (r = 0.51, p < 0.01) between the circulating levels of 7 S-collagen and ANP in all patients. The results of this investigation showed that increased circulating levels of ANP correlate with the abnormal metabolism of the vascular basement membrane observed in diabetic patients with microangiopathy.