BACKGROUND: Interstitial pneumonitis is an ill-defined side effect of sirolimus, a new immunosuppressant drug recently introduced for patients having organ transplantation. OBJECTIVE: To evaluate clinical and laboratory features of sirolimus-associated pneumonitis. DESIGN: Case series. SETTING: 1 transplantation center in Paris, France. PATIENTS: 24 patients who had renal transplantation and developed sirolimus-associated pneumonitis, including 8 patients previously reported. MEASUREMENTS: Symptoms; laboratory tests, including bronchoalveolar fluid analysis; and computed tomography (CT) of the chest. INTERVENTION: Withdrawal or dose reduction of sirolimus. RESULTS: Clinical symptoms included cough (23 patients), fatigue (20 patients), fever (16 patients), and dyspnea (8 patients). Computed tomography of the chest showed reticular and ground-glass opacities (4 patients), bronchiolitis obliterans-organizing pneumonia (19 patients), and lobar consolidation (1 patient). Bronchoalveolar lavage showed lymphocytic (19 patients) or eosinophilic (3 patients) alveolitis or pulmonary hemorrhage (2 patients). A reduction in the sirolimus dose resulted in transient clinical improvement in 2 patients, but discontinuation of drug therapy was eventually necessary in all patients. All patients recovered completely within 6 months. LIMITATIONS: The sirolimus trough level in patients from this single center was higher than that usually used in patients having renal transplantation. CONCLUSION: Lymphocytic alveolitis and radiologic bronchiolitis obliterans-organizing pneumonia are the key findings in sirolimus-associated pneumonitis. Sirolimus withdrawal was associated with recovery within 6 months.