It is well known that selenium is highly toxic to several species of mammals. Here we report the potential neurotoxicity of diselenides, as measured by the manifestation of seizures. The modulation of various neurotransmitter systems potentially involved in seizure episodes and death was also evaluated. The results of the present investigation suggest that toxicity of diselenides depends on the route of administration as well the species (rats or mice). These data show that modulation of more than one neuronal system can account for diselenide-induced seizures in mice. Additionally, changes in structure of diselenides, such as to introduce a functional group, influence the appearance of seizure episode. Conversely, all allosteric modulators tested did not protect dipropyl diselenide-induced seizures, indicating that aliphatic is more toxic than aromatic diselenides. Acute treatment with dipropyl diselenide inhibited [3H]-glutamate uptake to the crude synaptosomes. In contrast animals injected with diphenyl diselenide did not inhibit [3H]-glutamate uptake.