We studied the relationships between exercise (locomotion) and respiratory and circulatory responses in 19 cats that walked or ran normally on a treadmill, and in 16 paralyzed animals during fictive locomotion, i.e., locomotory activity in motor nerves to the legs. Preparations included anesthetized cats with intact brains and unanesthetized decorticate (hypothalamic) and decerebrate (mesencephalic) animals. Spontaneous actual locomotion and fictive locomotion occurred in all preparations except the mesencephalic cats. Electrical stimulation or injection of a GABA antagonist (picrotoxin) into the hypothalamic locomotor region caused locomotion to develop. In all cases when locomotion occurred, respiration and arterial pressure increased in proportion to the level of locomotor activity despite control or ablation of respiratory feedback mechanisms. Respiration and arterial pressure increased similarly during fictive locomotion despite the absence of muscular contraction or limb movement and the lack of change of metabolic rate. We conclude that the study provides experimental support for the feed-forward, or command signal, hypothesis for the genesis of proportional changes of respiration and circulation that occur during exercise. Feedback mechanisms are not required for its operation. We suggest that command signals emanating from the hypothalamus provide the primary drive for changes of respiration and circulation during exercise.