Analysis of lithium (Li+) in the brain and blood after intraperitoneal injection (i.p.) shows that initially its concentration is high in blood and negligible in the brain. Subsequently its concentration increases in the brain and disappears from the blood. Lithium itself affects neurological actions but the mechanisms remain obscure. It also modifies the toxic action of oxygen at high pressure (OHP), which causes convulsions, either suppressing or exacerbating it. These clearly separate effects correspond with the presence of Li+ in the blood (suppression) or in the brain (exacerbating). Determination of the effect of Li+ and OHP upon cations, catecholamines, ammonia, tyrosine hydroxylase, and monoamine oxidase in brain and blood tissue showed that there was very little correspondence between changes in the cations either with Li+ or the toxic effects of OHP. On the other hand, OHP developed a sustained blood and brain hyperammonemia in rats which could be negatively modified by Li+ in the blood. The latter effect also corresponded with a prolongation of convulsive latency. Changes in brain catecholamines, tyrosine hydroxylase, monoamine oxidase and tyrosine were effected by Li+ and potentiated by OHP. These data suggest that Li+ and OHP mediate their effects relatively more through developing hyperammoneic states in both blood and brain than by altering cation concentrations in these tissues.