Infection is a frequent complication and cause of death in renal failure, but the association between uremia, depressed immune status, and susceptibility to infection is far from proven. In the present studies, the effect of uremia on the inflammatory response and phagocytic ability was investigated in an animal model. The inflammatory response, as measured by the ability of leukocytes to mobilize into subcutaneous implanted sponges, was impaired at 6 hr but was normal 24 hr after implantation. The peripheral blood response of uremic animals to the leukocytosis promoting protein from Bordetella pertussis was similar to that of control animals. Reticuloendothelial clearance of labelled albumin was unimpaired but catabolism of this substance was reduced significantly in uremic animals. The ability of the uremic host to clear an intravenous challenge of virus was also depressed. Phagocytic and bactericidal capability of polymorphonuclear (PMN) leukocytes, measured in vitro by latex ingestion and phagocytosis and killing of Staphylococcus aureus, was normal. PMN phagocytic function in vivo was determined by the clearance of viable Escherichia coli from subcutaneously implanted sponges and no significant difference between control and uremic groups was found. These studies have further defined the effect of uremia on immune mechanisms and support our contention that uremia per se is not a major factor contributing to the compromised immune status in this host.