Recent macrolide derivatives, roxithromycin, azithromycin and clarithromycin show more favourable pharmacokinetic characteristics in comparison to old ones and some differences in antibacterial activity. With the aim of improving our understanding of some aspects of their action against respiratory pathogens, we determined the MICs and MBCs of Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, Moraxella catarrhalis and Haemophilus influenzae. Azithromycin was the most active agent against Haemophilus influenzae and Moraxella catarrhalis, while clarithromycin was more active against Streptococcus pneumoniae, Streptococcus pyogenes and Staphylococcus aureus with MICs similar to those of erythromycin. The bactericidal activity of all tested derivatives was weak against Staphylococcus aureus (MBC/MIC ratio approximately 16) and against Moraxella catarrhalis (MBC/MIC ratio, 8-16), but good against Staphylococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae (MBC/MIC ratio, 2-4). The determination of killing curves in the presence of 2 MIC and 10 MIC of azithromycin, clarithromycin and roxithromycin confirmed their weak bactericidal activity against Staphylococcus aureus and Moraxella catarrhalis as well as their effective activity against Streptococcus pyogenes and Streptococcus pneumoniae. Azithromycin showed the highest bactericidal activity against Haemophilus influenzae. As expected, the three derivatives produced a quite prolonged PAE when exposed to 5 MIC for 1 h, ranging between 2-4 h. The bactericidal activity and the prolonged PAE of new macrolides for the most common respiratory pathogens should assure a good clinical activity in respiratory infections including those sustained by Haemophilus influenzae, which is less susceptible to erythromycin and other old macrolides.