Suppression of ventilation by tasks such as talking may produce breathlessness in normal individuals under conditions when a strong respiratory drive exists, e.g., during exercise, and in patients with severe lung disease. To investigate the nature of breathlessness produced by a dissociation between ventilation and chemical drive, we studied ten naive normal subjects who breathed at various levels of ventilation while end-tidal PCO2 (PETCO2) was held at 55 mm Hg. After a 10-min equilibration period of free breathing at PETCO2 = 55 mm Hg, subjects used a visual target to adjust ventilation to five different levels ranging from 50% below to 50% above the chemically driven ventilation (CDV). Ratings of breathlessness were made on a visual analogue scale relative to the intensity of breathlessness experience at CDV. As ventilation was targeted to levels below CDV, all subjects became increasingly breathless; the response was more variable when ventilation was targeted to levels above CDV. Overall, the relationship between ventilation and breathlessness was described by a hyperbolic function, for which the coefficient of determination (R2) was 0.92. Ventilation was suppressed below CDV without recruitment of antagonistic muscles during inspiration. The intensity of breathlessness was not correlated with measures of respiratory effort. We conclude that suppressed ventilation is a useful model for the study of breathlessness not fully explained by measures of respiratory effort and we speculate that the dissociation between chemical drive and afferent signals produced by motion of the lung and chest wall is important in modulating the sensation of breathlessness.