The effect of a neurotoxic organometal, methyl mercuric iodide, and an aromatic solvent, toluene, upon the transmembrane potential (ψ), across both the limiting membrane of isolated nerve terminals and their mitochondria, has been studied. Exposure of nerve endings to either of these toxicants in vitro resulted in a dose-dependent diminution of ψ that was especially pronounced in the case of mitochondria. This was not prevented by a concurrent exposure to an antioxidant (α-tocopherol), or an iron chelator (deferoxamine), or ganglioside GM 1. No significant changes were detected in synaptosomal potentials derived from cortices of rats exposed to methyl mercury or toluene at levels known to increase the rate of formation of reactive oxygen species within this region. The especial vulnerability of mitochondrial ψ to these agents may be due to the disruption of oxidative phosphorylation and may be related to the increase in intrasynaptosomal free ionic calcium that both of these chemicals can induce.