The effects of folic acid on synaptic transmission in the hippocampal slice have been studied. Application of folic acid (0.1-1 mM) increased the size of population spikes recorded extracellularly in the CAl pyramidal cell layer and caused the appearance of multiple population spikes. Intracellular recording revealed that folic acid had no consistent effect on the membrane potential, but greatly reduced the rapid chloride-mediated phase of the inhibitory postsynaptic potential (IPSP) evoked by ortho- and antidromic stimulation. The slower, potassium-mediated phase of the IPSP was usually enhanced. Furthermore, folic acid abolished spontaneous IPSPs recorded with potassium chloride-filled microelectrodes. All of these effects were quickly reversible when the drug was washed from the chamber. Finally bath-applied folic acid reduced the hyperpolarization produced by iontophoretically applied GABA. Based on these results, we conclude that folic acid produces its excitatory effects on hippocampal pyramidal cells by a disinhibitory action which involves a postsynaptic blockade of GABA responses.