Neurophysiological methods fall into two broad categories, macrophysiological and microphysiological. The unit of analysis for microphysiological methods is cellular or subcellular (e.g. membrane or channel) whereas the unit of analysis for macrophysiological methods is a population of neurons. Each set of methods may be used to great advantage or disadvantage, depending upon the experimental question at hand. The purpose of the chapter is to focus on studies which have used macrophysiological methods to investigate the neurotoxicity produced by organometals. For each study to be discussed, the issues under consideration will be (1) appropriateness of the method to answer the experimental question; (2) adequacy of experimental design in using the method; (3) importance of the findings; and (4) identification of unresolved issues.