Acetylcholine (1muM) increased cyclid GMP content in paced perfused rat hearts within 15 sec., with peak content occurring at 1 min. No effect of acetylcholine on cyclic AMP content, phosphorylase activity or glycogen synthase was observed. Epinephrine (1muM) infusion increased both cyclic AMP content and phosphorylase, but did not alter cyclic GMP content or glycogen synthase activity. When acetylcholine was infused during the second min. of a 2 min. infusion of epinephrine, the cholinergic agent increased cyclic GMP and reduced the stimulated phosphorylase activity and elevated cyclic AMP.