Whilst chronic renal failure (CRF) patients are known to have an impaired immune response the explanation is unclear. We investigated the immunosuppressive effect of plasma from CRF patients on an in vitro assay of normal lymphocyte function. One hundred and sixty regular dialysis patients had significantly greater plasma suppressive activity (PSA) than that of normal healthy subjects. PSA decreased after haemodialysis but increased after blood transfusion. Renal allograft recipients with low PSA were more likely to have accelerated rejection. Assay of the functional capacity of plasma for inhibiting protease (e.g. plasmin, thrombin, trypsin) suggest that high PSA is associated with the excess formation of protease-inhibitor complexes and liberation of immunoregulatory peptide (less than 10,000 daltons).