The aim of this study was to examine differential sympathetic nerve responses in peripheral tissues during exercise. In decerebrate rats, we examined renal and lumbar (which innervates hindlimb) sympathetic nerve activities (RSNA and LSNA, respectively) during: 1-min rhythmic (1- to 4-s stimulation-to-relaxation) contraction of the triceps surae muscles; rhythmic stretch; and rhythmic contraction with hindlimb ischemia. During these interventions, the RSNA and LSNA responded synchronously as tension was developed. In both rhythmic contraction (n=10, +465±40 g in tension) and muscle stretch (n=10, +506±36 g), the RSNA response was significantly greater than the LSNA response (+109±19 vs. +75±11% P<0.05 in contraction and +99±16 vs. +55±11% P<0.05 in stretch from baseline). Hindlimb ischemia (n=7) enhanced both the RSNA and LSNA responses to contraction by 18% and 33% (P<0.05), respectively. The data demonstrate that the RSNA responses to muscle stretch and contraction are greater than those seen with LSNA. We suggest that the differential sympathetic outflow induced by the muscle afferents activation contributes to the distribution of cardiac output observed during exercise. Moreover, ischemic metabolites produced in contracting muscle likely sensitizes the muscle afferents engaged by contraction and stretch. Supported by NIH R01 HL075533 (JL) and R01 HL078866 (JL) and R01 HL060800 (LIS).