Previous studies have led to the revival of the hypothesis that breathlessness is the perception of respiratory muscle effort and is present when the tension developed by muscles increases, when the muscles are weak, or when both conditions are present simultaneously. Using a category scale, the intensity of breathlessness was measured in 20 subjects (2 normal subjects and 18 patients) undergoing an incremental exercise test (50 to 100 kpm/min) to maximal capacity. The patients were selected to provide a heterogeneous group of pulmonary diseases, obesity, muscular weakness, and cardiac disease, with a wide variability in exercise capacity (250 to 1,900 kpm/min) and severity of dyspnea. Maximal inspiratory pressure (MIP), pleural pressure (Ppl), the extent of shortening of the inspiratory muscles as indicated by the tidal volume expressed as a percent of vital capacity (VT/VC), the rate of shortening as indicated by flow rate, the frequency of contraction as indicated by breathing frequency (fb), and the duty cycle (TI/Ttot) were measured throughout exercise to assess their relative contribution to the intensity of breathlessness. Using multifactorial analysis, the perception of breathlessness was significantly (p less than 0.01) related to the Ppl, inspiratory flow rate (VI), VT/VC, TI/Ttot, and fb. A multiple linear regression equation that included all these variables explained 69% of the variance, with no single factor being identified as uniquely predominant: Breathlessness = 3.0 (Ppl/MIP) + 1.2 (VI) + 4.5 (VT/VC) + 0.13 (fb) + 5.6 TI/Ttot) - 6.2 (R = 0.83). The intensity of effort required to produce a given pressure increases when the muscle is weak, when the velocity of contraction increases, or when the muscle shortens.(ABSTRACT TRUNCATED AT 250 WORDS)