The action of tetrahydro-9-aminoacridine (THA) on guinea pig pyramidal neurons was examined using intracellular recording in an in vitro hippocampal slice preparation. THA had a powerful excitatory action on pyramidal neurons, causing depolarization, increased firing, and an increase in input resistance. This excitatory action of THA persisted in atropine and in tetrodotoxin. The estimated reversal potential of this THA effect was near -90 mV. These results indicate that THA has a direct excitatory action on pyramidal neurons independent of its anticholinesterase activity, resulting from blockade of a conductance carried predominantly by potassium ions.