Clinical hypokalaemia is associated with acquired electrocardiographic QT prolongation and arrhythmic activity initiated by premature ventricular depolarizations and suppressed by lidocaine (lignocaine). Nevertheless, regular (S1) pacing at a 125 ms interstimulus interval resulted in stable waveforms and rhythm studied using epicardial and endocardial monophasic action potential (MAP) electrodes in Langendorff-perfused murine hearts whether under normokalaemic (5.2 mM K+) or hypokalaemic (3.0 mM K+) conditions, in both the presence and absence of lidocaine (10 microM). Furthermore, the transmural gradient in repolarization time, known to be altered in the congenital long-QT syndromes, and reflected in the difference between endocardial and epicardial MAP duration at 90% repolarization (DeltaAPD(90)), did not differ significantly (P > 0.05) between normokalaemic (5.5 +/- 4.5 ms, n = 8, five hearts), hypokalaemic (n = 8, five hearts), or lidocaine-treated normokalaemic (n = 8, five hearts) or hypokalaemic (n = 8, five hearts) hearts. However, premature ventricular depolarizations occurring in response to extrasystolic (S2) stimulation delivered at S1S2 intervals between 0 and 22 +/- 6 ms following recovery from refractoriness initiated arrhythmic activity specifically in hypokalaemic (n = 8, five hearts) as opposed to normokalaemic (n = 25, 14 hearts), or lidocaine-treated hypokalaemic (n = 8, five hearts) or normokalaemic hearts (n = 8, five hearts). This was associated with sharp but transient reversals in DeltaAPD(90) in MAPs initiated within the 250 ms interval directly succeeding premature ventricular depolarizations, from 3.3 +/- 5.6 ms to -31.8 +/- 11.8 ms (P < 0.05) when they were initiated immediately after recovery from refractoriness. In contrast the corresponding latency differences consistently remained close to the normokalaemic value (-1.6 +/- 1.4 ms, P > 0.05). These findings empirically associate arrhythmogenesis in hypokalaemic hearts with transient alterations in transmural repolarization gradients resulting from premature ventricular depolarizations. This is in contrast to sustained alterations in transmural repolarization gradients present on regular stimulation in long-QT syndrome models.