The adhesion of human platelets to the human arterial subendothelium was investigated using everted postmortem renal arteries after the first bifurcation and reconstituted blood containing 51Cr-labelled, aspirin-treated platelets in a perfusion chamber according to Baumgartner. The accumulation of 51Cr on the arterial segment was a reliable reflection of the number of platelets that adhered. The dependence of platelet adhesion on platelet number, perfusion time, haematocrit and perfusion rate were found to be similar to what was observed with rabbit aorta previously, notwithstanding the essentially different nature of the human subendothelium, with its layers of smooth muscle cells above the internal elastic lamina. The system was used to study the role of factor VIII-von Willebrand factor (VIII-VWF). VIII-VWF was found to be the only plasma factor enhancing adhesion of platelets to the vessel wall. No suggestion of an inhibitory substance in plasma was found. Double perfusion experiments indicated that VIII-VWF binding to subendothelium supported subsequent platelet adhesion. A good correlation was found between the amount of VIII-VWF bound and platelet adhesion. Comparison of binding of albumin, fibrinogen, 7-globulin and VIII-VWF showed that VIII-VWF bound less. This suggests that VIII-VWF does penetrate less easily in the subendothelium, which is in agreement with immunofluorescence studies of tissues. Studies with washed platelets not treated with aspirin showed parallelism between accumulation of VIII-VWF and platelet deposition in thrombi. These data may be explained by assuming a non-easily exchangeable pool of VIII-VWF on the platelet surface and increased binding of VIII-VWF to platelets in thrombi.