"Dyspnea" refers to the awareness of breathing discomfort that is typically experienced during physical activity in health and across a broad spectrum of disease. In various patient populations, dyspnea is a significant independent predictor of hospitalization, disability and death; and contributes significantly to exercise intolerance and an impaired health-related quality-of-life. Nevertheless, the causes of dyspnea remain poorly understood. As a result, dyspnea is often a difficult symptom for health care providers to manage and treat. Therefore, the general aim of this research program is to advance our understanding of the mechanisms of activity-related dyspnea. Studies will be performed in healthy, young adults to test the hypothesis that the intensity, quality and unpleasantness of dyspnea is determined by the interaction between an increased drive to breathe and the ability of the respiratory system to meet this demand. Detailed physiological and perceptual responses to strenuous exercise performed on a stationary bicycle will be examined and compared under experimental conditions designed to increase the drive to breath, disturb the response of the respiratory system or both in combination. Additional studies will seek to (i) isolate the role of nerves located in the lungs, airways and breathing muscles and (ii) clarify the role of the central nervous system in shaping the expression of activity-related dyspnea. The results of these studies will provide valuable insight into the mechanisms of exertional dyspnea in health and disease. This information is critical if we are to develop, refine and implement more effective interventions to relieve dyspnea in various patient populations.