A controversial issue in exercise physiology is the relative contribution of central command versus afferent input from contracting muscles and baroreceptors in the regulation of sympathetic nerve activity (SNA) during exercise. Recent studies of exercising humans have suggested that central command increases cutaneous sympathetic sudomotor nerve activity but have challenged the concept that central command contributes importantly to increases in sympathetic vasoconstrictor nerve activity to skin and skeletal muscle. The purpose of this study was to examine the influence of central command on renal SNA and lumbar SNA during spontaneous locomotion in decorticate cats. Unanesthetized decorticate cats that developed locomotion spontaneously or during electrical stimulation of the subthalamic locomotor region were studied in the presence and absence of input from skeletal muscle and baroreceptor afferents. Spontaneous rhythmic locomotion in the unparalyzed state was associated with significant increases in mean arterial pressure (MAP) from 106 +/- 10 to 133 +/- 11 mm Hg (p less than 0.05) and increases in renal SNA of 301 +/- 100% (p less than 0.05). During spontaneous fictive rhythmic locomotion in paralyzed cats, there were also significant (p less than 0.05) increases in MAP (43 +/- 6%), renal SNA (183 +/- 32%), and lumbar SNA (223 +/- 83%). Baroreceptor denervation did not attenuate increases in MAP, renal SNA, and lumbar SNA during locomotion. During electrical stimulation of the subthalamic locomotor region in paralyzed cats, MAP increased by 43 +/- 17% (p less than 0.05), and renal SNA increased by 175 +/- 47% (p less than 0.05). These findings indicate that central command is capable of increasing sympathetic neural drive in unanesthetized decorticate cats. This increase in sympathetic drive occurs even in the absence of feedback from contracting muscles or from arterial and cardiopulmonary baroreceptors.