Protein C was determined in 42 patients with terminal uremia and 20 healthy controls in three different ways 1) anticoagulant activity 2) amidolytic activity 3) antigen level. Protein C anticoagulant activity was markedly decreased in uremia, but was partly normalized during hemodialysis treatment, whereas the amidolytic activity and antigen level of protein C were normal and without changes during dialysis. The activities and antigen levels of factor II and X were normal before and after hemodialysis. In anticoagulated patients we found a good correlation between prothrombin levels and protein C levels determined with three different assays. We did not find any evidence for a defect carboxylation of protein C as the cause for the defective protein C in uremia. The BaCl2 precipitation in the Protein C anticoagulant assay was incomplete both in uremia and in controls but without differences between the two groups. In vitro addition of urea and creatinine did not decrease protein C activity. The cause of the defective protein C in uremia is still not known but it might contribute to thromboembolic complications.