Objective: To investigate protein concentration changes during venous occlusion of proteins with reported affinity for extracellular matrix (plasminogen activator inhibitor type 1, antithrombin III, fibronectin and von Willebrand factor) in comparison with proteins with no reported affinity (albumin, tissue-type plasminogen activator, immunoglobulin G, fibrinogen, α2-macroglobulin, immunoglobulin M) in insulin-dependent diabetic patients with and without diabetic nephropathy. Design: Cross-sectional study. Setting: Outpatient diabetic clinic in a tertiary hospital. Subjects: Insulin-dependent diabetic patients without diabetic nephropathy (normoalbuminuria, n = 17), patients with incipient diabetic nephropathy (n = 19), and patients with diabetic nephropathy (n = 13). Non-diabetic subjects served as a control group (n = 14). Results: For plasminogen activator inhibitor type 1 and fibronectin we found a smaller increase in protein concentration after venous occlusion in diabetic patients with nephropathy than in patients without nephropathy (1.7 (- 3-5.8) vs 3.2 (- 0.4-8.7) ng/ml, P < 0.05; 0.01 (- 0.23-0.05) vs 0.05 (0-0.13) g/l, P < 0.01 respectively). Remarkably, von Willebrand factor showed a decrease in patients with nephropathy - 0.27 (- 0.6-0.38) vs - 0.01 (- 0.33-0.25) lU/ml, P < 0.01. Proteins with no reported affinity for extracellular matrix increased in a similar way in patients with and without nephropathy (albumin 9 (3-12) vs 10 (5-19) g/l; tissue-type plasminogen activator 3.6 (0.8-21.7) vs 4.1 (0-10.8) ng/ml; immunoglobulin G 1.9 (0.6-4.9) vs 2.6 (1.6-8.9) g/l; fibrinogen 30 (9-60) vs 34 (- 38-77)%; α2-macroglobulin 52 (- 44-102) vs 48 (- 68-90)% and immunoglobulin M 0.40 (0.11-0.78) vs 0.30 (- 0.11-0.75) g/l). The changes in protein concentration during venous occlusion did not depend on the molecular weight or charge. Conclusion: Proteins with reported affinity to extracellular matrix show a smaller increase during venous occlusion in patients with nephropathy compared with patients without nephropathy. This may reflect changes in the vascular wall in insulin-dependent diabetic patients with nephropathy.