The ability of polymorphonuclear leucocytes (PMNs) from elderly healthy subjects and post-operative cancer patients to ingest and killClostridium difficile was studied. The percentage of phagocytosis in clinically healthy subjects aged 69–82 years ranged from 20.2±3.2 (mean±SD) to 34.1±4.2, depending on the strain ofC. difficile, from 6.7±2.2 to 11.2±2.2 in post-operative cancer patients aged 65–69, and from 68.4±3.1 to 81.1±6.3 in young healthy control subjects. In both study groups, the defect was in part serum-associated. Although the total number of bacteria killed by the PMNs was reduced in the two study groups, the percentage of ingested bacteria killed by the PMNs was similar to that in the young healthy subjects. These differences were not noted whenEscherichia coli andStaphylococcus aureus were used as the test organisms. The defective PMN function againstC. difficile in the elderly and post-operative cancer patients described in this study may offer an explanation as to why these individuals are at high risk of developing antibiotic-associated colitis.