Background: Little is understood about the characteristics of dyspnea in patients with interstitial lung disease (ILD), and its severity is likely influenced by multiple factors. Depression and functional status are known to influence dyspnea in patients with COPD. The aim of this study was to determine the relationship of dyspnea with clinical parameters, including depression and functional status, in patients with ILD. Methods: Dyspnea was measured with the Baseline Dyspnea Index and the University of California San Diego Shortness of Breath Questionnaire. Clinical parameters were recorded. Regression analysis was performed to determine independent correlates of dyspnea. Results: Fifty-two subjects were enrolled. The two dyspnea scales were strongly correlated (r = -0.79; P < .00005). The mean levels of dyspnea were 6.5 and 41.0, representing a moderate degree of dyspnea. Clinically meaningful depressive symptoms were found in 23% of subjects. Independent correlates of dyspnea severity for each dyspnea scale were depression score (P = .002 and P < .0005), 4-m walk time (P = .001 and P = .06), FVC (P = .07 and P = .004), and diffusing capacity of the lung for carbon monoxide (P = .007). BMI had borderline significant association with the Baseline Dyspnea Index (P = .10). Conclusions: In patients with ILD, dyspnea is associated with depression score, functional status, and pulmonary function. These results suggest that attention to depression and functional status is important in these patients and that treatment directed at these comorbidities may improve dyspnea and quality of life. Trial registry: ClinicalTrials.gov; No.: NCT00611182; URL: www.clinicaltrials.gov. © 2011 American College of Chest Physicians.