Metabolic changes of basement membrane proteins, collagenous and non-collagenous, will be followed by morphological changes and develop into diabetic microangiopathy. In this study, serum concentrations of laminin and type IV collagen were measured in 87 cases o f non-insulin-dependent diabetes mellitus (NIDDM) and examined with the development of diabetic nephropathy and retinopathy. Serum type IV collagen was measured by two methods, assays of the 7S portion (7S-RIA) and of both the 7S and central triple helical domain (IV-EIA). IV-EIA showed more significant elevation with development of diabetic microangiopathy than 7S-RIA and laminin. After measurement of basement membrane proteins, 66 cases were followed clinically for 3 or 4 years. In 45 cases without worsening of diabetic nephropathy, IV-EIA and laminin concentrations in serum were significantly lower than those in 21 cases who showed worsening of diabetic nephropathy in the same period, Multivariate analysis revealed a good model including three dependent variables of serum values of laminin, IV-EIA and mean blood pressure for discriminating between the worsened group and the non-worsened group. High values of IV-EIA and laminin in serum may be useful in predicting the worsening of diabetic nephropathy.