This study examined the transduction pathways activated by epinepherine in the pacemaker region of the toad heart. Recordings of membrane potential, force, and intracellular Ca²⁺ concentration ([Ca²⁺]_i) were made from arrested toad sinus venosus. Sympathetic nerve stimulation activated non--, non--adrenoceptors to evoke a membrane depolarization and a transient increase in [Ca²⁺]_i. In contrast, the -adrenoceptor agonist isoprenaline (10 µM) caused membrane hyperpolarization and decreased [Ca²⁺]_i. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM) mimicked the isoprenaline-evoked membrane hyperpolarization. Epinephrine (10-50 µM) caused an initial membrane depolarization and an increase in [Ca²⁺]_i followed by membrane hyperpolarization and decreased [Ca²⁺]_i. The membrane depolarizations evoked by sympathetic nerve stimulation or epinephrine were abolished either by the phospholipase C inhibitor U-73122 (20 µM) or by the blocker of D-myo-inositol 1,4,5,-trisphosphate-induced Ca²⁺ release, 2-aminoethoxydiphenyl borate (2-APB, 60 µM). Neither U-73122 nor 2-APB had an affect on the membrane hyperpolarization evoked by -adrenoceptor activation. These results suggest that in the toad sinus venosus, two distinct transduction pathways can be activated by epinephrine to cause an increase in heart rate.