Background: Clarithromycin exhibits anti-inflammatory as well as antimicrobial activity, leading to decreased symptoms of asthma and chronic sinusitis. The mode of anti-inflammatory effects of clarithromycin on inflammatory cells is not well understood. We hypothesized that clarithromycin inhibits inflammatory cell mediator release and survival. Methods: We investigated the effects of this drug on survival and mediator release from mast cells, eosinophils and neutrophils. Results: Human eosinophil and neutrophil respiratory burst was inhibited by up to 54% after 1–2 h pretreatment with 100 µg/ml clarithromycin. Similar doses of erythromycin did not affect respiratory burst responses in these cells. Clarithromycin at doses of up to 100 µg/ml had no effect on granule-derived mediators released from mast cells and neutrophils. However, we found that clarithromycin (100 µg/ml) induced cell death in mast cells and eosinophils after 16–48 h incubation. Conclusion: Clarithromycin inhibited inflammatory cell mediator release and survival, which may enhance its ability to reduce the symptoms of chronic sinusitis and asthma.