In guinea pig hippocampal slices, stimulation of stratum radiatum during depolarization (with intracellular current injections) of nonspiking cells (presumed to be glia) in the apical dendritic area of CA1 pyramidal neurons resulted in a subsequent long-term potential of intracellularly recorded excitatory postsynaptic potentials as well as extracellularly recorded population spikes in the CA1 area. Tetanic stimulation of stratum radiatum resulted in a subsequent prolonged depolarization of the presumed glial cells, and this depolarization was smaller when the tetanus was given during the presence of 2-amino-5-phosphonovalerate or when the slices were exposed to Ca2+-free medium containing Mn2+ and Mg2+. These results suggest that glial depolarization is involved as one of the steps in generating long-term potentiation.