The phagocytic, bactericidal, and metabolic activities of monocytes from patients with congenital neutropenia were not significantly different than the activities of monocytes from patients with cyclic neutropenia or chronic infections. However, significant differences in metabolic, phagocytic, and bactericidal functions were found between monocytes from any source and normal neutrophils. During phagocytosis, monocytes produced more of the bactericidal product hydrogen peroxide than did neutrophils. However, monocytes in suspension had decreased phagocytic capacity compared to neutrophils and killed staphylococci less well. Moreover, monocytes had a diminished capacity to iodinate ingested bacteria. Quantitation of granular myeloperoxidase activity revealed that monocytes had a relative deficiency of this enzyme, which could explain the decreased iodination and killing of ingested bacteria by monocytes when compared to neutrophils. These findings offer an explanation for the failure of compensatory monocytosis to protect the host from bacterial infection when neutrophil reserves are diminished.