The Neurotoxicology program aims to develop sensitive markers of human toxic exposures that would be particularly hazardous to the nervous system. Both behavioral and biochemical markers are being developed. One promising approach employs brief, objective tests of neurobehavioral function that can be used both in field studies with humans, including children, and with laboratory animals. The test is noninvasive and thus can be administered repeatedly to humans at their homes or workplace for health surveillance. The ability to apply these neurobehavioral tests to both humans and animals improves confidence in extrapolating results from experiments that can only be done with animals, e.g., the examination of histopathological and neurochemical changes in the brain which are the criteria for neurotoxicity. These behavioral markers can document the role of environmental toxins in developmental disabilities such as lead-related deficits in learning of children. A promising biomarker is glial fibrillary acidic protein (GFAP), which increased in the monkey brain during exposure to trimethyl lead and in the rat brain soon after exposure to methylmercury. We detected GFAP in brain and CSF of rats, and in brains of pigeons, fish and nonhuman primates. Thus, GFAP is a very promising marker because it is present in most species of animals of interest as laboratory models or environmental sentinels. In rats and pigeons, GFAP is an early indicator of exposure to neurotoxicants (cadmium, methylmercury, acrylamide) but not to chromium, which appears to lack specific neurotoxicity. GFAP and related proteins of neuronal tissue origin will be examined in CSF and in peripheral blood as markers of cellular and functional changes in the nervous system. These neurotoxicologic assays are being integrated with the ecological projects, where proteins in the brains of wild fish and birds can serve as markers for biological impact of ecological pollution. Finally, this project continues to provide the entire program with detailed evaluations of the oral exposures used with rats so as to identify potential confounding factors such as reduced water consumption or body weight.