The early positive cortical evoked potential to somatosensory stimuli is regularly increased in amplitude in patients receiving lithium carbonate treatment. This may reflect a unique neurochemical effect of lithium since similar changes have not been observed in humans following other drugs. To investigate this finding, cortical evoked potentials to peripheral somatosensory stimulation were obtained in rats and cats with implanted epidural electrodes. In rats, increasing doses of oral lithium chloride, up to 5 meq/kg/d which approached the LD 50, produced no reliable change in the early positive evoked response amplitude. In cats, an increased amplitude of the early positive-negative cortical potential was observed in every instance and the serum lithium levels were within the range used clinically in humans. The increased cortical evoked response amplitude in cats did not directly correlate with serum lithium levels but was delayed 1 to 5 days after serum lithium levels reached their peak. The findings in cats are similar to the human studies. The negative results observed in rats may reflect important species differences regarding lithium.