The effect of endogenously released and exogenously administered acetylcholine on potassium uptake was studied in the sinus node of the guinea pig under different conditions. The results suggest the following conclusions : (1) acetylcholine is released in small amounts in the sinus node perfused in vitro and more so during electrical stimulation; (2) when the muscarinic receptors are blocked, an inhibitory action of endogenously-released acetylcholine on potassium uptake is revealed; (3) the inhibition requires small concentrations of acetylcholine, for 10-5 mol/1 eserine, by preventing acetylcholine hydrolysis, turns the inhibition into a stimulation of potassium uptake; and (4) the inhibitory action of acetylcholine on potassium uptake can be reproduced by administering small amounts of exogenous acetylcholine.