Removal of extracellular Ca2+ induced transient outward currents (Io) at membrane potentials more positive than 0 mV in the guinea pig cardiac cell. This current reached a peak within a few milliseconds of stimulation, then decreased exponentially. External Cd2+ (0.1 mM) mimicked the inhibitory effect of Ca2+ on Io. Addition of D 600 (1 microM) or quinidine (0.1 mM) in the perfusate produced a reversible suppression, and replacement of internal K+ with tetraethylammonium induced a complete inhibition of Io. The steady-state inactivation of the transient component of Io was expressed by a Boltzmann relation with a half-inactivation voltage of -33.5 mV and a slope factor of 7.5 mV. This transient component was completely or almost completely inhibited by substitution of 4-aminopyridine for external cations. We conclude that in guinea pig cardiac cells, extracellular Ca2+ at physiological concentrations is masking the activity of an A-type K+ channel. This finding implies that even should a channel gene or transcript be identified using molecular biological techniques, the channel may not necessarily function under physiological conditions.