S 16257 is a new bradycardic agent. Its electropharmacological profile has been compared to that of the known bradycardic compound UL‐FS 49 (Zatebradine). Intracellular recordings of action potentials (APs) were performed with conventional glass microelectrodes. In the rabbit isolated sino‐atrial node (SAN) tissue, S 16257 and UL‐FS 49 (1 μ m , 3 μ m and 10 μ m ) were equipotent in slowing spontaneous APs firing predominantly by decreasing the rate of diastolic depolarization (at 3 μ m , – 23.8 ± 3.9% and – 27.9 ± 2.6%, respectively). For the two compounds a maximal effect was obtained at 3 μ m . In these preparations, action potential duration at 50% of total repolarization (APD 50 ) was more affected by UL‐FS 49 than S 16257 at any concentration tested (at 3 μ m , + 8.9 ± 2.9% and + 29.1 ± 3.7% for S 16257 and UL‐FS 49, respectively; P ≤ 0.01). To estimate the direct effects on AP duration, driven cardiac preparations were exposed to these agents. In guinea‐pig papillary muscles, paced at a frequency of 1 Hz, increasing concentrations of S 16257 or UL‐FS 49 (0.1 to 10 μ m , 30 min exposure for each concentration) slightly prolonged AP repolarization. This prolongation was more marked for UL‐FS 49 (at 1 μ m , + 6.1 ± 0.6% and + 11.2 ± 1.3% elevation of APD 50 , for S 16257 and UL‐FS 49, respectively). Application of UL‐FS 49 (3 μ m ) to rabbit Purkinje fibres, triggered at a frequency of 0.25 Hz, induced a marked prolongation of APD 50 and APD 90 (+ 149.4 ± 51.2% and + 86.0 ± 15.4%, respectively). S 16257 (3 μ m ) induced only a weak prolongation of AP (+ 14.1 ± 5.0% and + 14.8 ± 3.3% for APD 50 and APD 90 , respectively) significantly smaller than in the case of UL‐FS 49. These results show that S 16257 slows the rate of spontaneous AP firing in isolated SAN mainly by a reduction of the diastolic depolarization of the cells, which suggests an inhibition of the pace‐maker current ( I f ). S 16257 and UL‐FS 49 are equipotent in their bradycardic effect but S 16257 is more specific as it induces less increase in myocardial repolarization time.