The antiepileptic drug valproic acid (VPA) reduces the occurrence of the rhythmic and synchronous bursts produced by hippocampal neurons maintained 'in vitro' and bathed in Ringer-containing low-Ca2+ (0.2 mM), high-Mg2+ (4.0 mM). In this medium, synaptic transmission is blocked, thus demonstrating an action of VPA unrelated to potentiation of GABAergic phenomena. This conclusion is reenforced by the persistence of VPA effects in the presence of bicuculline. Also, the VPA doses effective in reducing the low-calcium synchronous burst in the hippocampal slice are similar to the free plasma levels of VPA observed to exert anticonvulsant effects in kindled rats.