A body of evidence highlights the fact that macrolides may not only enhance the host defence system through increased cytokine synthesis by host cells but also exhibit anti-inflammatory activity by including anti-inflammatory cytokines. Several authors have stressed the possibility that macrolides are useful in the treatment of asthma because of their antimicrobial activity rather than any anti-inflammatory action. However, the mechanism of action of macrolides in improving asthma and reducing airway responsiveness is speculated not to be due to their antibiotic properties, especially when these agents are active in noninfectious asthma. The steroid-sparing effect of macrolide antibiotics has been postulated to contribute to their beneficial actions in the treatment of asthma. Nevertheless, a number of studies have shown that macrolides antibiotics have an anti-inflammatory effect which is independent of their antibiotic action or any influence on corticosteroid metabolism. Macrolides may be useful in the treatment of patients with steroid-dependent asthma, probably because they inhibit eosinophilic inflammation. It has also been suggested that the effect of macrolides on bronchial hyperresponsiveness is mediated by their inhibitory action on superoxide production and chemotaxis of polymorphonuclear neutrophils and the mixed lymphocyte reaction. In any case, it is clear that the mechanism of action of macrolides in asthmatic syndrome is not unequivocal. Only well-designed and -conducted clinical studies are capable of assessing the efficacy and safety of immunosuppressive macrolides in the treatment of asthma.