This paper reviews the influence of the type of capillary bed, type of compartment, and the presence of active transport systems, on the pharmacokinetics of antimicrobial agents in tissues and fluids of the body. In the absence of active transport or local degradation, the mean concentration or 'area under the curve' of free (unbound) drug in ordinary extravascular sites over the dosing interval at equilibrium is equal to that in the serum. Because the latter is easily measured, there should be no need to measure tissue concentrations except in unusual circumstances. Among the factors that will alter the relationship described above are active transport, pH partition, and bulk flow. Antibiotics such as the macrolides, lincosamines and quinolones may accumulate in high concentrations in cells containing lysosomes. There is some evidence that the intracellular sites may serve as a reservoir from which these drugs may later be released into tissue fluids, a phenomenon not taken into account in the relationships described above. Although knowledge of the in-vitro activity and local concentrations of antibiotics is of use in predicting therapeutic activity, many factors which are difficult to quantify in a given instance make precise correlations impossible. The inability of antibiotics alone to sterilize abscesses is probably not due to a problem in antibiotic penetration but to insusceptibility of the organisms and inefficacy of the phagocytes in an abscess. Similar processes operate to reduce the efficacy of antibiotics when treatment is delayed.