Leukocyte differential counting by flow cytochemistry has shown 28 subjects with partial or complete neutrophil myeloperoxidase (MPO) deficiency in a population of about 60 000 patients screened at a general hospital. Partial (13 patients) or complete (13 patients) MPO deficiency was confirmed by examination of cytochemical stains in 26, biochemical measurement of total enzymatic activity in eight, and flow cytometry in six patients. None had apparent hematologic disorders. Only four patients had infections; of these, two had major systemic infections (one, candidiasis; one, bacteremia). In assays of leukocyte function only minor defects in killing of Staphylococcus aureus by MPO-deficient cells were noted whereas killing of Candida albicans was much more impaired. Family studies in eight patients have shown various degrees of partial or complete MPO deficiency in first-degree relatives of six. The findings indicate that the incidence of MPO deficiency is much higher than previously suspected. Although MPO appears to be necessary for killing of Candida species by neutrophils, the importance of its role in normal antibacterial defense must be re-evaluated.