Intracellular penetration, accumulation and disposition are important parameters governing the activity of antibiotics against intracellular bacteria. Beta-lactams diffuse into but do not accumulate in phagocytes, probably because of their acidic character. Aminoglycosides are too polar to pass across membranes and are therefore only taken up slowly by endocytosis, which results in an exclusively lysosomal localization. Lincosaminides, macrolides and fluoroquinolones all accumulate in phagocytes, the two former classes of drugs showing both a cytosolic and a lysosomal localization. Fluoroquinolones appear to be entirely soluble in cells. Analysis of their activity in a model of Staphylococcus aureus-infected J774 macrophages has revealed low activity of clindamycin, whereas macrolides, and even more so fluoroquinolones, easily reduce the original inoculum.