Rat hippocampal tissue slices were made hypoxic in control medium and in medium containing the ion channel blockers tetraethylammonium (TEA), 4-aminopyridine (4-AP), or tetrodotoxin (TTX). Postsynaptic evoked potentials, extracellular DC potential Vec, and in some experiments extracellular potassium concentration [K+]o were monitored in stratum pyramidale of the CA1 region. TEA (10 mM) decreased the latency of hypoxia-induced spreading depression (SD), and reduced the amplitudes of the changes in Vec and [K+]o. 4-AP (50 microM) also decreased the latency of SD but had no effect on the Vec shift. In most slices, TTX (1 microM) increased SD latency but had no effect on the Vec shift. In some slices, TTX blocked the occurrence of SD.