Rationale: Lung clearance index (LCI) measured by the nitrogen multiple breath washout (MBW), is a noninvasive measure of ventilation inhomogeneity that has been shown to be elevated in patients with primary lung disease. Objectives: To assess whether LCI, Scond (convection-dependent ventilation inhomogeneity) and Sacin (diffusion-convection dependent inhomogeneity) from the MBW are elevated in patients with connective tissue disease related lung disease and to ascertain whether MBW is feasible in this patient population. Methods: 19 patients with connective tissue disease (1 with mixed connective tissue disease, 4 with rheumatoid arthritis (RA) and 14 with RA and associated lung disease) completed spirometry, MBW and health-related quality of life (HRQoL) questionnaires at a single study visit. A separate group of 8 healthy controls also completed spirometry and MBW at a single visit. Results: MBW was repeatable and feasible in the majority of patients. LCI and Sacin were significantly raised in patients with RA related lung disease compared to healthy controls (LCI 9.43 verses 7.36, p=0.008; Sacin 0.2320 verses 0.0568, p=0.004). Significant correlations were seen between MBW parameters and HRQoL. Conclusion: MBW is a feasible and repeatable and may be a promising technique in the assessment of lung disease in patients with rheumatoid arthritis. LCI and Sacin appear to be potentially the most useful with significant differences seen between healthy controls and patients with rheumatoid arthritis related lung disease. These pilot findings support the further investigation of MBW in this patient population and provide data for sample size calculations for future studies.