Single atrial cells from guinea pig heart were voltage-clamped using the whole-cell configuration of the patch-clamp technique under conditions in which most of the ionic and exchange currents known in cardiac cells were minimized. Extracellular 5 or 50 μM ATP activated a CI−current, in addition to a rapidly desensitizing cation-selective current. A nonhydrolyzable ATP analogue, adenosine-5'-O-(3-thiotriphosphate) (50 μM), also evoked these two currents, indicating involvement of purinoceptors rather than ecto-ATPase on the membrane. ADP, AMP, and adenosine were also effective in inducing the CI−current, showing no clear order of potency for the purinoceptor subtypes involved. The purinoceptor-activated CI−current, like the β-catecholamine-cAMP-dependent cardiac CI−current, showed outward rectification and time independence.