Adenosine (Ado), like acetylcholine (ACh), hyperpolarizes and shortens the atrial action potential (AP). To elucidate the underlying mechanism of Ado and ACh actions, intracellular APs and membrane currents were measured in calcium-tolerant single myocytes isolated from guinea pig atria. Both Ado and ACh hyperpolarize the resting membrane to the potassium equilibrium potential (Ek) and cause a marked abbreviation of the AP. Analysis of membrane currents reveal that Ado and ACh increase the steady-state currents. The Ado- and ACh-induced current reverses polarity at -92 mV, a value that corresponds well with a calculated EK of -90 mV. Thus the Ado- and the ACh-sensitive current can be interpreted as a potassium current. It is suggested that Ado, like ACh, increases the potassium conductance via a common mechanism.