Tetraphenylphosphonium (TPP+) accumulation in rat brain synaptosomes was measured in the presence of various stimuli. TPP+ accumulation was sensitive to an increase of extracellular K+ or to the presence of Na+ channel neurotoxins. Examination of the effects of drugs with different physico-chemical properties on TPP+ accumulation showed that there was no effect under low and high K+ conditions; pimozide, flunarizine and buterizine were active in the presence of veratridine or scorpion venom. These results were compared to data obtained for the specific binding of [3H]BTX-B, a selective marker for the Na+ channel. It can be concluded that certain drugs, although active on [3H]BTX-B binding, are not necessarily identified when TPP+ is used as probe.