Evidence is presented which suggests that the mechanism of action of the myeloperoxidase-H₂O₂-Cl⁻ antimicrobial system in the phagocyte is by the formation of aldehydes. Aldehyde production resulting from myeloperoxidase-mediated decarboxylation and deamination of alanine was quantitated with 20,000-g granules from guinea pig polymorphonuclear leukocytes serving as the enzyme. Equimolar quantities of acetaldehyde and CO₂ were obtained. There was an absolute requirement for both H₂O₂ and Cl⁻ for decarboxylation by the myeloperoxidase-containing granules. The myeloperoxidase-H₂O₂-Cl⁻ system decarboxylated both d- or l-alanine equally and had a pH optimum of 5.3. Decarboxylation of l-alanine by intact guinea pig polymorphonuclear leukocytes was increased 2.5-fold by phagocytosis. Guaiacol peroxidation by the granules was inhibited 90% in the presence of Cl⁻ at acid pH. Under these conditions, decarboxylation and deamination of amino acids by myeloperoxidase were significantly stimulated, resulting in aldehyde production. Taurine, a competitive inhibitor of amino acid decarboxylation, inhibited bactericidal activity of the myeloperoxidase-H₂O₂-Cl⁻ system but had no effect on the myeloperoxidase-H₂O₂-I⁻ bactericidal system. Since the myeloperoxidase-H₂O₂-I⁻ system does not participate in amino acid decarboxylation, its mechanism of antimicrobial action appears to be different from that found with Cl⁻.