Very brief and intense exercise triggers a biphasic metabolic and respiratory response with a second phase that occurs after the cessation of the muscular activity. The effects on minute ventilation (V˙E) produced by manipulation of the peripheral circulation in metabolically active muscles could thus be studied without the confounding effects of painful contractions. The second phase of breath-by-breath V˙E and pulmonary gas exchange responses to a brief change in work rate (400 W for 12 s) were studied in six healthy male subjects on four occasions (24 tests). An upper thigh cuff inflation was randomly applied either above or below the systolic blood pressure (200 or 90 Torr, respectively) for 90 s just after the cessation of the contractions prior to the delayed rise in pulmonary gas exchange (eight tests in each subject). Total occlusion produced a significant reduction in the delayed rise in V˙E (-29 ± 3 %) which normally occurred 20-25 s after the cessation of the contractions. In contrast, cuff inflation at a level predominantly impeding venous return while partially maintaining the arterial supply reduced the rise in pulmonary gas exchange in similar proportion to that during total obstruction but with a slight but not significant reduction in ventilation (-9 ± 5 %). V˙E during partial occlusion was if anything higher than in control tests with similar oxygen uptake (280 W), despite a higher blood pressure (BP) during occlusion (+7 Torr). It is concluded that the factors resulting from a reduction in venous return or from the involvement of the arterial baroreflex are not responsible for the changes in V˙E produced by the obstruction of the circulation to and from metabolically active muscles. It is proposed that factors related to the level of the perfusion pressure in hyperaemic muscles, possibly located at the venular end of the microcirculation, could account for the changes in V˙E observed. Experimental Physiology (2001) 86.6, 759-768.