Azithromycin achieves high concentrations in phagocytic cells and in fibroblasts. The newer macrolides also have this property but the intracellular penetration of azithromycin in relation to extracellular concentration is particularly notable. As a weak base, azithromycin is thought to concentrate in lysosomes of phagocytes and fibroblasts but many in vitro factors such as pH and temperature also affect the uptake process. Uptake of azithromycin by polymorphonuclear leucocytes results in an intracellular/extracellular concentration ratio of approximately 40 after one hour of incubation. Intraphagocytic antimicrobial activity has been demonstrated but is rather less than might be anticipated from the intracellular concentrations that are reached. Importantly, the high antibiotic levels found intracellularly do not appear to disrupt normal phagocyte function. Although azithromycin levels in the blood are low soon after administration, tissue concentrations are high and sustained. It appears that fibroblasts serve as a reservoir of drug in tissue, allowing activity against organisms and possibly transferring antibiotic to phagocytic cells for activity against intracellular pathogens and delivery to infection sites.