Inactivation of a range of antibiotics acting at different points in the metabolism of the bacterial cell was detected by estimating the MIC and MBC in the presence of liver and other tissue preparations. High temperature treatment and sonication of liver cells increased their ability to inactivate antibiotic action. This treatment would have almost completely destroyed enzyme activity, which was, therefore, not thought likely to be the cause of the phenomenon. The loss of antibiotic activity may be related to "protein binding" and a dialysis experiment showed that penicillin binding with liver homogenate was very much greater than with human albumin. It may be that increased disruption of tissue cells by physical methods exposes more active binding sites which reduces the bioavailability of antibiotics. Some degree of binding specificity was indicated in experiments in which DNA was shown to block antibiotics acting primarily on DNA--related synthesis and RNA blocked antibiotics acting on RNA--related metabolism. Suggestions are made for the cause of failure of antibiotic treatment in certain clinical situations.