The azalide azithromycin, which is derived from erythromycin, contains a methyl-substituted nitrogen in the lactone ring. This 15-membered expanded lactone ring results in improved acid stability and oral bioavailability compared with erythromycin. Azithromycin possesses a broad spectrum of activity against Gram-positive and Gram-negative bacteria, including enhanced activity compared with the macrolides against Haemophilus influenzae and Moraxella catarrhalis. In vitro activity of azithromycin against intracellular and clinically atypical pathogens is also good. Azithromycin has a distinct pharmacokinetic profile compared with other antimicrobial agents, the most prominent feature is its high tissue selectivity. Concentrations of azithromycin in respiratory tract, gynaecological tissue and prostate remain above minimum inhibitory concentrations of pathogens for several days, thus making it possible to use a short-course, once-daily dosing regimen. Another feature of azithromycin is that it rapidly penetrates phagocytic cells, with the release of the antibiotics at local sites of infection. Comparative clinical trials have shown that azithromycin given once daily for 3 or 5 days is comparable to comparator drugs given for 7 or 10 days in the treatment of otitis media, sinusitis, pharyngitis, acute bronchitis, acute infectious exacerbations of chronic bronchitis, community-acquired pneumonia and skin and soft tissue infections in adults. Azithromycin given once daily for 3 days has also been shown to be effective in the treatment of respiratory tract and skin and soft tissue infections in children. In addition, some sexually-transmitted diseases are effectively treated by a single 1-g dose of azithromycin; clinical and microbiological responses were comparable to those recorded using doxycycline given twice daily for 7 days. The short-duration, once-daily dosing regimen is well tolerated in adults and children, and there is no evidence of interaction between azithromycin and theophylline, terfenadine, or cimetidine.