The purpose of this study was to further document the role of locally released norepinephrine (NE) in the control of metabolic and endocrine responses to exercise in rats. Post-ganglionic blockade with bretylium (20 mg.kg-1, i.v.) reduced NE release from sympathetic nerve endings and triggered a compensatory increase in epinephrine (E) release from the adrenal medulla, as reflected by plasma NE and E concentrations at rest and exercise (E/NE ratio = 2.92 +/- 0.53 and 2.48 +/- 0.51 vs 0.62 +/- 0.15 and 1.48 +/- 0.18 in control rats; mean +/- SE). Following bretylium administration a reduction in running time to exhaustion (28 m.min-1, 8% slope: 33 +/- 2 min vs 74 +/- 10 min) was associated with 1) a faster decrease in blood glucose concentration (3.58 +/- 0.80 mM vs 8.09 +/- 0.38 mM in control rats exercised for 33 min); and 2) an increased glycogen store utilization in fast-twitch muscles (superficial vastus lateralis and gastrocnemius lateralis). Glycogen utilization was not modified in soleus muscle and in the liver. Taken together these results suggest that post-ganglionic blockade increased carbohydrate store and peripheral blood glucose utilization. This could reflect an impairment in fat mobilization and utilization which might be secondary to a reduction of NE release in the adipose tissue and/or in the endocrine pancreas.