Whole-cell patch-clamp recordings were made from substantia nigra pars reticulata (SNR) neurones in rat midbrain slices to characterise the presynaptic action of cannabinoids on GABA neurotransmission and to study the involvement of calcium channels. The cannabinoid agonist WIN55212-2 at 10 microM reduced the amplitudes of GABA(A) receptor mediated spontaneous postsynaptic currents (IPSCs). This effect was fully reversed by the selective cannabinoid CB1 receptor antagonist SR141716A (20 microM). WIN55212-2 also caused a reduction in the evoked IPSC amplitude, which was associated with a significant increase in the paired pulse ratio over a 50 ms interval. In addition, the reduction in spontaneous IPSC amplitude by WIN55212-2 could be largely occluded by the presence of extracellular Cd2+ (200 microM). These observations suggest that cannabinoids exert a presynaptic inhibition on GABAergic transmission to SNR neurones via CB1 receptor, an action which involves inhibition of Cd2+-sensitive presynaptic Ca2+ channels.