The effect of secretin on forearm metabolism (muscle compartment) was examined in the presence of low and high concentrations of insulin. Continuous infusions (30 min. duration) of secretin 12 ng/min. (SEC), insulin 160 ng/min. (INS) or these doses of insulin and secretin together (INS + SEC) were delivered into the brachial arteries of normal volunteers. SEC alone was without significant effect on forearm metabolism. INS as previously reported, stimulated glucose and potassium uptake and inhibited the output of some amino acids from the deep venous bed. The two hormones together (INS + SEC) increased maximum lactate (p less than 0.025) and alanine output (p less than 0.005) beyond that observed with INS alone. A marked calcium output occurred (p less than 0.001) with the combined infusion which was not observed with either hormone alone. Potassium metabolism with INS + SEC was similar to that observed with INS alone. These results suggest that these two hormones, acting in concert, stimulate glycolysis and net calcium efflux. This joint action of insulin and secretin may have a physiological role in the immediate postprandial period.