The hippocampal formation and its cholinergic input are an important neurobiological substrate for learning and memory processes. Since alterations in learning and memory are a common consequence of toxicant exposure it is possible that the hippocampus is an important target site for neurotoxicity. In fact, the hippocampus has been shown to be preferentially susceptible to a wide variety of toxic insults. For example, the hippocampus is damaged by environmental toxicants such as heavy metals, drugs of abuse such as alcohol and by cerebrovascular insufficiency finally resulting in hypoxia. The NMDA subtype of glutamatergic receptor plays a major role in learning and memory and in excitoxicity secondary to ischemia, hypoglycemia and trauma. The nature of the adverse effects of neurotoxins at this receptor site may be linked to the neurobiological characteristics that make this structure uniquely susceptible to toxic insult.