The efficacy of macrolides against extracellular pathogens depends on extracellular levels of free drug and the organisms' patterns of susceptibility to the macrolides. The effect of macrolides against most bacteria is considered time-dependent. The size of inoculum affects erythromycin's activity against streptococci and, moreover, against staphylococci. The optimal effect is observed at a pH of 8. A significant postantibiotic effect (PAE), lasting approximately 9 hours, has been shown with erythromycin and roxithromycin against gram-positive cocci. Azalides share the same properties. For the streptogramin synercid, a dose-dependent bactericidal activity within a range of low concentrations has been demonstrated. The serum area under the curve appeared to be the best predictor of in vivo effect on the mouse thigh model. Synercid also exhibited a prolonged PAE (approximately 10 hours) against the main pathogens of its spectrum. A better knowledge of the pharmacodynamic properties of macrolides and streptogramins is essential for definition of proper dosing regimens.