We examined the effects of epinephrine (25, 50, and 150 nM) on 1) basal and insulin-stimulated 3-O-methylglucose (3-MG) transport in perfused rat muscles and 2) GLUT-4 in skeletal muscle plasma membranes. Insulin increased glucose transport 330-600% in three types of skeletal muscle [white (WG) and (RG) gastrocnemius and soleus (SOL)]. Glucose transport was also increased by epinephrine (22-48%) in these muscles (P < 0.05). In contrast, the insulin-stimulated 3-MG transport was reduced by epinephrine in all three types of muscles; maximal reductions were observed at 25 nM epinephrine in WG (-25%) and RG (-32.5%). A dose-dependent decrease occurred in SOL (-27% at 25 nM; -55% at 150 nM, P < 0.05). Insulin (20 mU/ml) and epinephrine (150 nM) each translocated GLUT-4 to the plasma membrane, and no differences in translocation were observed between insulin and epinephrine (P > 0.05). In addition, epinephrine did not inhibit insulin-stimulated GLUT-4 translocation, and the combined epinephrine and insulin effects on GLUT-4 translocation were not additive. The increase in surface GLUT-4 was associated with increases in muscle cAMP concentrations, but only when epinephrine alone was present. No relationship was evident between muscle cAMP concentrations and surface GLUT-4 in the combined epinephrine and insulin-stimulated muscles. These studies indicate that epinephrine can translocate GLUT-4 while at the same time increasing glucose transport when insulin is absent, or can inhibit glucose transport when insulin is present.