Phagocytic, chemotactic, and oxidative metabolic capacity of circulating neutrophils was studied in 20 patients with Crohn's disease. In vitro tests of chemotaxis and phagocytosis of isolated neutrophils from patients did not differ from that of healthy controls. However, superoxide anion production by phorbol-myristate-acetate and formylmethionyl-leucyl-phenylalanine-stimulated neutrophils from patients with Crohn's disease was significantly diminished compared with controls. Measurement of cytochrome b559 in total membranes of neutrophils from patients showed that it was significantly lower than in controls. Disease activity did not correlate either with the production of superoxide anion or with the cytochrome b559 content. It is concluded that oxidative metabolism is impaired in neutrophils from patients with Crohn's disease and that this defect could be caused by a reduced content in membrane b-type cytochrome. Although this defective neutrophil function may contribute to granuloma formation, other factors have to be implicated in disease inflammatory activity.