The present study investigated differences in symptom perception between a clinical sample with medically unexplained symptoms (MUS) and a matched healthy control group. Participants (N = 58, 29 patients) were told that they would inhale different gas mixtures that might induce symptoms. Next, they went through 2 subsequent rebreathing trials consisting of a baseline (60 s room air breathing), a rebreathing phase (150 s, which gradually increased ventilation, PCO2 in the blood, and perceived dyspnea), and a recovery phase (150 s, returning to room air breathing). Breathing behavior was continuously monitored, and dyspnea was rated every 10 s. The within-subject correlations between dyspnea on the one hand and end-tidal CO2 and minute ventilation on the other were used to index the degree to which perceived dyspnea was related to specific relevant respiratory changes. The results showed that perceived symptoms were less strongly related to relevant physiological parameters in MUS patients than in healthy persons, specifically when afferent physiological input was relatively weak. This suggests a stronger role for top-down psychological processes in the symptom perception of patients with MUS.