36 unrelated individuals with neutrophil MPO deficiency, (10 totally MPO deficient) were found on screening a population of 148,000 subjects. A further 2 subjects with total and 22 with partial MPO deficiency were identified through family studies. The assessment of neutrophil function, i.e., peroxidase activity, superoxide anion generation, microbicidal activity towards fungi and bacteria, and locomotor behaviour, was carried out in 10 subjects with total and 4 with partial MPO deficiency. We found that the enzyme defect is associated with a marked impairment in the killing of both S. aureus and C. albicans, without affecting microbicidal activity against S. faecalis. There appears to be a high incidence of malignancy in patients with complete MPO deficiency, suggesting a relationship between a defective MPO system and neutrophil-mediated tumor cell cytotoxicity.