Roots of Delphinium denudatum W. are used for the treatment of epilepsy by traditional healers in subcontinent. Aqueous fraction (AF) isolated from D. denudatum has previously shown significant anticonvulsant activity in in vivo and in vitro models of seizures. We investigated anticonvulsant effects of AF on pentylenetetrazole (PTZ) and bicuculline (BIC)-induced epileptiform activity in primary hippocampal neuronal cultures. Electrophysiological studies on single pyramidal neurons were carried out by using whole-cell current clamp technique. Introduction of AF (0.6 mg/ml) in perfusate blocked PTZ (10 mM) and BIC (100 micro M)-induced epileptiform activity comprising of paroxysmal depolarization shifts (PDS). The PDS were elicited again when AF was removed from perfusate. We conclude that AF contains anticonvulsant compounds that possibly interact with GABA(A) receptor to produce blockade of epileptiform activity. Further studies on isolation of compounds from AF may lead to discovery of new class of anticonvulsants.