The effects induced by arachidonic acid upon excitatory synaptic transmission were investigated in the CA1 subfield of rat hippocampal slices. Perfusion with medium containing 50 microM of arachidonic acid induced in 12 of 19 experiments a long-lasting potentiation of the stratum radiatum-induced responses recorded in the cell body and in the apical dendritic layers. In 5 of 19 experiments, arachidonic acid evoked a depression of the same responses. Both effects were antagonized by nordihydroguaiaretic acid which is an inhibitor of lipoxygenase enzymes. These results demonstrate that one or more than one of the arachidonic acid metabolites of the lipoxygenase pathways might be involved in the long-term modulation of synaptic transmission in the hippocampus.