The objective of this study was to investigate the serum level of the 7S domains of type-IV collagen [IVc(7S)] and its relations with microangiopathy in non-insulin-dependent diabetes mellitus (NIDDM). This study comprised 73 patients with NIDDM that were consulted in our outpatient clinic. Among the 73 NIDDM patients, 43 with normal arterial pressure were selected to assess the relationship between serum levels of 7S collagen and microangiopathy. There was a significant relationship between the serum IVc(7S) levels and the presence of retinopathy and nephropathy. These findings suggest that an increased IVc (7S) concentration may reflect the abnormal collagen metabolism of the vascular basement membrane in NIDDM patients. Column chromatography of the NIDDM patients' sera revealed the heterogeneity of immunoreactive type-IV collagen (7S) and showed that these domains were composed mainly of degradation products of type-IV collagen. These data suggest that degradation of IVc is accelerated in the vascular basement membrane of NIDDM patients.