Performance on the Neurobehavioral Evaluation System (NES) has been demonstrated to be affected by exposure to a variety of neurotoxicants. However, the relation of NES subtests to CNS function has not yet been documented in patients diagnosed with neurologic disorders known to implicate specific brain substrates. A validation study of the NES2 was carried out in patients with multiple sclerosis (MS) and Parkinson's disease (PD), disorders exhibiting neuropathology at loci (white matter in MS, basal ganglia in PD) believed to be the sites of action of several known neurotoxicants. The results indicated that performance on certain NES2 subtests was affected in expected ways in both types of patients. However, performance on many more subtests was impaired, relative to controls, in MS than in PD. The relative insensitivity to PD suggests that expansion and refinement of the battery are required if it is to serve well in detecting the effects of toxicants in subjects without frank physical symptoms. These are the goals of a new version of the instrument currently under development (NES3).