BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the leading cause of late mortality after lung transplantation. METHODS: We added azithromycin (AZI) (250 mg/day for 5 days, followed by 250 mg every other day) to the current immunosuppressive therapy in eight lung transplant recipients (mean age 36 years) with established BOS in an attempt to prevent further decline of the forced expiratory volume in 1 sec (FEV1). RESULTS: Before the administration of AZI, there was a gradual decline of the FEV1 (-34.4%+/-14.7%) compared with the patients' best postoperative values. Twelve weeks after AZI had been added, there was a significant increase in the FEV1 (+18.3%+/-14.6%, P <0.0001, analysis of variance) with an absolute increase of 328+/-305 mL. This increase persisted in three patients during 9 months of follow-up. CONCLUSIONS: AZI is a promising drug for some patients with BOS after lung transplantation. The exact mechanism of action is unknown at the present time.