The concentrations of amino acids and calcium were measured in the subarachnoid cerebrospinal fluid (CSF) of rats prior to, and following, profound hypoglycemia. Calcium concentrations fell and amino acid changes were non-specific following hypoglycemia. In particular, elevations in excitatory amino acids did not occur, even though typical neuropathologic changes were found. These data do not support a role for excitatory amino acids or calcium as a 'CSF-borne toxin' in hypoglycemic brain injury. Moreover, the histopathological patterns of cell loss in the dentate gyrus often could not be reconciled with the concept of a CSF-borne toxin.