Background: Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM. Methods: Sirolimus (trough level 5 - 10 ng/ml) was administered to ten female patients (42.4 +/- 11.9 years) with documented progression. Serial pulmonary function tests and six-minute-walk-distance (6-MWD) assessments were performed. Results: The mean loss of FEV(1) was - 2.30 +/- 0.52 ml/day before therapy and a significant mean gain of FEV(1) of 1.19 +/- 0.26 ml/day was detected during treatment (p = 0.001). Mean FEV(1) and FVC at baseline were 1.12 +/- 0.15 l (36.1 +/- 4.5%pred.) and 2.47 +/- 0.25 l (69.2 +/- 6.5% pred.), respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated (3 months Delta FEV(1): 220 +/- 82 ml, p = 0.024; 6 months Delta FEV(1): 345 +/- 58 ml, p = 0.001); (3 months Delta FVC: 360 +/- 141 ml, p = 0.031; 6 months Delta FVC: 488 +/- 138 ml, p = 0.006). Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy. Conclusions: Our data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.