The role of thiamine in the etiology of human diseases is being investigated. Despite reports from other laboratories which suggested that glyoxylic acid may play a role in such processes, we have found no convincing evidence that this C-2 compound is involved. We have found, however, that thiamine deficiency does result in marked changes in the levels of some important free amino acids in various regions of the brain. We are using various biochemical, tissue culture, and neurochemical techniques to elucidate the mechanism and effects of such changes.