The respiratory burst activity (generation of hydrogen peroxide) of peripheral polymorphonuclear leukocytes (PMN) in both phorbol myristate acetate (PMA)-stimulated and unstimulated states and phagocytosis were assessed using flow cytometry on 46 patients with chronic renal failure: 33 patients undergoing chronic hemodialysis (CHD), 8 patients who have never been on dialysis (nonhemodialysis; NHD), 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD); these patients were compared with 27 normal control subjects. In patients just before the initiation of dialysis, impaired hydrogen peroxide production by PMA-stimulated PMN and depressed phagocytosis were noted, which was restored to the control levels by hemodialysis. A mild but significant reduction of hydrogen peroxide production in a PMA-stimulated state was found in NHD patients, and an inverse correlation was noted between the impairment of this function and the degree of diminished renal function. There was no significant difference between CAPD patients and controls in hydrogen peroxide production by PMA-stimulated PMN. Decreased hydrogen peroxide production by unstimulated PMN was observed in both CHD and CAPD patients. These findings may explain, at least partly, the enhanced susceptibility to bacterial and fungal infections of these patients.