The effects of serotonin (5-HT) as well as 5-HT(1A) and 5-HT(4) receptor agonists, (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) and zacopride, respectively, on population spikes evoked by electrical stimulation and on spontaneous epileptiform activity were investigated in CA1 area of hippocampal slices. Spontaneous epileptiform activity was recorded from slice in a nominally Mg(2+)-free medium. While 5-HT application resulted in a decrease of population spikes evoked in standard incubation conditions, in accordance with earlier studies, it exerted two opposite effects on epileptiform activity. The early inhibitory effect was mimicked by 8-OH-DPAT while the later, excitatory, by zacopride. The application of 8-OH-DPAT decreased, and that of zacopride increased, the amplitude of population spikes. A comparison of the dose-dependence of the excitatory and inhibitory effects of serotonergic agonists on the amplitude of the population spike and on the frequency of epileptiform discharges indicated that the latter is a more sensitive measure of the activation of 5-HT(1A) and 5-HT(4) receptors than the former. Thus, spontaneous epileptiform activity recorded in a nominally Mg(2+)-free slice medium represents a convenient model for investigation of hippocampal neuronal reactivity to the activation of various 5-HT receptor subtypes.