Four of 22 specimens of human pus inactivated up to 90% of added penicillin within one hour in vitro. Ampicillin and cephaloridine were also inactivated, but streptomycin and fusidic acid were not. The effect was not related to the protein content of the pus, nor to its pH value. Microbes that may produce beta-lactamase in small quantities were isolated from three of the four specimens, but the enzyme was not detected in the pus by physical methods nor by microbiological inhibition assay. The inactivating effect was shown to be a property of the solid portion of the pus, and was absent from the filtrate. We suggest that the effect may be an intrinsic property of the host, which should be investigated further as it has important implications for clinical practice.