No studies of cystic fibrosis (CF) have systematically characterized the evolution of the qualitative dimensions of exertional dyspnea. Adults with CF (n = 25) and control individuals matched for sex, age, and body mass index (n = 25) underwent cardiopulmonary cycle exercise testing with a detailed evaluation of ventilatory and dyspnea responses. The qualitative dimensions of dyspnea were examined during each exercise stage by having subjects select phrases that best described their breathing (i.e., "work/effort," "unsatisfied inspiration," and "unsatisfied expiration"). Subjects also selected phrases that described the quality of their breathing at peak exercise using an established 15-item questionnaire, which was then clustered into different categories. Subjects with CF had greater ventilatory requirements, higher end-inspiratory and end-expiratory lung volumes (% total lung capacity), and an earlier inflection/plateau in tidal volume during exercise compared with control subjects. Increased work/effort was the dominant qualitative descriptor in both groups throughout exercise. Unsatisfied inspiration was selected by 48% of subjects with CF and 40% of controls at some point during exercise. The onset of unsatisfied inspiration in these subjects occurred at a significantly lower relative exercise intensity in subjects with CF vs. controls (72 ± 21 vs. 94 ± 11% Wmax, P < 0.01). Chest tightness was the only qualitative descriptor cluster that was selected more frequently by subjects with CF vs. controls (36 vs. 0%, respectively, P < 0.05) at peak exercise. Therapeutic interventions that reduce ventilatory requirements and improve lung volumes may delay the onset of distressing sensations such as unsatisfied inspiration and chest tightness in adults with CF.