In the rat and mouse, GABAergic neurones of the substantia nigra pars reticulata (SNr) constitute the primary output of the basal ganglia. The intrinsic high frequency spiking of SNr GABAergic neurones tonically inhibits the thalamus and superior colliculus. Relief of this tonic inhibition is critical for movement. Previous work in rats has demonstrated that both Na+ and Ca2+ inward currents are responsible for spike initiation and repolarization is partially controlled by the small conductance Ca2+-dependent K+ channels (Atherton and Bevan, 2005). Here, we have investigated the presence of rapidly inactivating A-type K+ channels in SNr GABAergic neurones of the mouse. Midbrain slices containing SNr were prepared from adult mice (6 to 12 weeks old). In whole-cell recordings, SNr GABAergic neurones were physiologically distinguished from dopaminergic neurones by the absence of a hyperpolarization-activated inward current. Incremental depolarising voltage steps were applied from a holding potential of -100 mV in tetrodotoxin (100 nM) to block voltage-gated Na+ channels. Rapidly inactivating outward currents that had a half-activating voltage of -7.5 ± 2.8 mV (n = 10) and an inactivation time constant of 21.3 ± 4.6 ms at -10 mV (n = 9) were observed. The transient outward current at -10mV was inhibited by 4-aminopyridine (1 mM; 76 ± 12%, n = 4). The 4-aminopyridine-sensitive current had an inactivation time constant of 37 ± 14 ms at -10 mV (n = 3). These properties are consistent with A-type K+ currents, indicating that these channels may be important regulators of high frequency tonic firing and back-propagation of action potentials in SNr GABAergic neurones.