Aim: To determine serum and sputum Caveolin-1 (Cav-1) levels and their associations with transforming growth factor-beta (TGF-beta) and interstitial lung disease (ILD) in systemic sclerosis (SSc). Methods: Serum and induced sputum samples from 55 patients with SSc, 25 asthma patients and 16 healthy volunteers (HC) were tested for Cav-1 and TGF-beta by the ELISA technique. As a possible downstream signaling regulator of TGF-beta, Endothelin-1 (ET-1), a potent profibrotic protein, was also measured in all serum and sputum samples and relations with Cav-1 and TGF-beta were sought. All scleroderma patients were evaluated for their clinical and laboratory parameters. Pulmonary function tests (PFT) and high resolution computerized tomography (HRCT) were performed for the diagnosis of ILD. The alveolitis-fibrosis index and the SSc disease severity scores were noted for each patient. Results: Serum Cav-1 levels were lower in SSc compared to HC (p<0.01). Cav-1 levels were significantly lower in the sputum of SSc patients compared to both control groups (p<0.001). It was also found significantly lower in SSc-ILD compared to those without ILD (0.19 +/- 0.04 vs 0.25 +/- 0.07, respectively, p<0.01). Although no difference was found in the serum TGF-beta levels among the groups, sputum TGF-beta levels correlated positively with the alveolitis index (r=0.34) and correlated inversely with FVC measurements (r=-0.44, p<0.05) among SSc patients. Serum ET-1 was significantly higher in SSc patients (p<0.01) but no association was found between ET-1 and Cav-1 or TGF-beta. Conclusion: These results suggest that decreased sputum Cav-1 levels is associated with SSc related-ILD. Its use as a marker for the detection of SSc-ILD warrants further evaluation.