The glycoprotein laminin, a cross-shaped complex of three genetically different polypeptide chains, is a structural component of the capillary basement membrane. Serum laminin concentrations of healthy controls (n = 60) and adult type I diabetic patients (n = 170) were not age-dependent. Laminin was correlated with hemoglobin A1 (HbA1) values in normoalbuminuric patients (rs = .33, P < .0005, n = 116). Type I diabetic patients without nephropathy or retinopathy in good metabolic control had normal laminin levels. However, increasing stages of microangiopathy were associated with higher laminin levels. The molecular size distribution of serum laminin of control subjects (n = 4) and type I diabetic patients (n = 15) was analyzed by molecular-sieve chromatography. Laminin was eluted in two peaks with a molecular mass of 900 and 300 kd, most likely representing intact laminin and its P1 fragment, respectively. The areas of the two peaks were determined by two-gaussian function fitting. In patients without microangiopathy in poor metabolic control, an increase in the high-molecular weight (HMW) fraction could be detected as compared with healthy subjects and patients with acceptable metabolic control. Furthermore, the HMW laminin fraction and the ratio between the areas of the first and second peak increased with the stage of nephropathy (P < .001, Jonckheere-Terpstra test). These results provide evidence that (1) laminin concentration is increased in chronic hyperglycemia, (2) laminin may be a marker of microangiopathic lesions, and (3) elevated laminin levels may reflect an increased synthesis and/or a defective incorporation of laminin into the capillary basement membrane.