Increased incidence of infection in uraemic patients is mainly caused by granulocyte dysfunction. Recently we discovered a granulocyte inhibitory protein (GIP I) in the ultrafiltrate of haemodialysis patients, that inhibits four fundamental functions of polymorphonuclear leukocytes (PMNLs). We now report on the isolation of a further polypeptide in end-stage renal disease patient ultrafiltrate using a polyamide filter with biological activity inhibiting healthy PMNL function in vitro. This protein (GIP II) has a molecular weight of about 9500 Da. In-vitro nanomolar concentrations inhibit PMNL O2- production and glucose uptake stimulated by phorbol-myristate-acetate (PMA), but not by formyl-methionyl-leucyl-phenylalanine (FMLP). In-vitro studies were performed to compare the effects of GIP I and GIP II on several PMNL functions. In contrast to GIP II, GIP I inhibits only FMLP-, but not PMA-stimulated PMNL glucose uptake. The NH2 terminal amino acid sequence (21 amino acids) of GIP II shows homology to beta 2-microglobulin. Commercially available intact beta 2-microglobulin had no effect on PMNL glucose uptake and O2- production. The beta 2-microglobulin homologue protein isolated from plasma ultrafiltrates of uraemic patients cross-reacts with three different commercially available assays for intact beta 2-microglobulin. Therefore, beta 2-microglobulin levels measured in the plasma ultrafiltrates of regular haemodialysis patients are overestimated with contribution of an uncertain amount of the beta 2-microglobulin homologue protein (GIP II).