Propionibacterium acnes, the target of inflammation in acne, was tested for its sensitivity to the bactericidal and degradative functions of human polymorphonuclear leukocytes (PMN), monocytes, and their fractions. P. acnes strains were not killed by PMN under any conditions and were variably killed by monocytes in the presence of serum from acne patients. Control strains of Staphylococcus aureus and Micrococcus lysodeicticus were susceptible to both PMN and monocyte killing. P. acnes strains were also not killed by lysozyme, chymotrypsin, H2O2, human serum, PMN granule lysate, and PMN and monocyte cell lysates. The organism was sensitive to the bactericidal activity of myeloperoxidase in acid pH. In addition, P. acnes was shown to be relatively resistant to the degradative action of PMN and monocyte lysates, whereas M. lysodeicticus, S. aureus, and Staphylococcus epidermidis were all degraded to various degrees. The moieties that were liberated from P. acnes by PMN enzymes were predominantly low in molecular weight (1,000 to 25,000) and were consistent with cell wall fragments.