Fowler (Fowler, W.S., 1954, J. Appl. Physiol. 6:539-545) showed that rebreathing, despite worsening PCO2 and O2 saturation, relieved the distress of breathholding; he suggested a role for vagal input in the relief. We studied effects on respiratory sensation of breathholding and rebreathing in normals, patients with bilateral lung transplants (LT), who have a decrease in number of pulmonary stretch receptors (PSR), and heart transplant recipients (HT). Subjects held their breath until distress became intolerable, rebreathed various combinations of CO2 and O2, then performed another maximal breathhold. Respiratory distress was rated continuously (visual analog scale) by each subject. Both LT and HT had earlier onset of and more rapidly developing distress during breathholding, resulting in shorter breathhold times, than normals. Relief with rebreathing was neither as rapid nor as great in LT as in HT and normals. Our findings suggest that mechanisms that produce respiratory distress in HT and LT are similar, but differ from normals. However, reduction in distress on rebreathing is more rapid and greater in HT and normals than in LT. This is compatible with the loss during rebreathing of the inhibitory effect of PSR input on neural mechanisms that lead to respiratory distress.