In ultrafiltrated plasma (molecular weight less than 50,000) obtained from four patients with multiple muscular trauma and acute post-traumatic renal failure, it was possible to verify a subcomponential specific digestion of the subunits alpha and gamma of phosphorylase kinase isolated from rabbit skeletal muscle. The activity of free proteolytic enzymes in ultrafiltrated plasma as well as an increase of plasma alpha 1-antitrypsin values were correlated with the severity and unfavourable course of the illness. In contrast, the plasma levels of alpha 2-macroglobulin were drastically lowered. The mean total protein concentration in the sera of patients with post-traumatic ARF was lowered, whereas the mean ultrafiltrate protein concentration was significantly enhanced. In ultrafiltrated plasma of two patients with hyperuricaemic ARF, three patients with ARF after drug over-dosage, one patient with acute pancreatic necrosis combined with acute renal failure and one patient with chronic pancreatitis, no proteolytic activity could be detected using phosphorylase kinase as substrate. Studies on the trypsin binding capacity of the plasma protease inhibitors revealed a significantly lowered level in patients with post-traumatic acute renal failure as compared to healthy controls, patients with chronic renal insufficiency and patients on regular dialysis treatment Proteolytic activity was found in ca. 100-fold concentrated diafiltrates (molecular weight greater than 10,000) of patients on regular dialysis treatment. Our data suggest a participation of proteases on protein catabolism in hypercatabolic states. Whilst the blood coagulation system can largely be excluded as a source of proteases, it is possible that proteolytic enzymes may be released from muscle lysosomes and/or macrophages after multiple muscular trauma.