The aim of this study was to identify some of the mechanisms which could be involved in the blunted ventilatory response (V E) to exercise in the supine (S) position. The contribution of 1- the recruitment of different muscle groups 2- the activity of the cardiac mechanoreceptors, 3- the level of arterial baroreceptor stimulation and 4- the hemodynamic effects of gravity on the exercising muscles, was analyzed during upright (U) and S exercise. The delayed rise in VE and pulmonary gas exchange following an impulse like change in work rate (supra-maximal leg cycling at 240 W for 12 seconds) was measured in seven healthy subjects and six heart transplant patients both in the U and S positions. This approach allows the study of the relationship between the rise in VE and oxygen uptake without the confounding effects of the contractions of different muscle groups. These responses were compared to those triggered by an impulse like change in work rate produced by the arms which were positioned at the same at the same level of the heart in the S position and in the U position to separate the effects of gravity on the post exercising muscles from those on the rest of the body. Despite superimposable V and V responses, the delayed VE response following the leg exercise was significantly lower in the S posture than in the U position for each control subject and cardiac transplant patient (- 2.58 ± 0.44 l/min and - 3.52 ± 1.11 l/min respectively). In contrast, when the impulse exercise was performed with the arms, the reduction of the ventilatory response in the S posture reached at best one third of the deficit following the leg exercise and was always associated with a reduction in V of similar magnitude. It is concluded that the reduction in the VE response to exercise in the S position is independent of the types (groups) of muscles recruited and is not critically dependent on afferent signal originating from the heart, but seems to rely on some of the effects of gravity on the post-exercising muscles.