Recent studies show that GABAA-receptors mediated responses in the hippocampal cells are suppressed upon increases in intracellular Ca2+ [Ca2+]i. A series of experiments were carried out to evaluate the physiological significance of this modulatory action of [Ca2+]i. We show that GABAA-responses are suppressed by a preceding NMDA application in hippocampal cells. Furthermore the suppressive effect is mediated via an increase in [Ca2+]i. Additional data reveal that NMDA application suppressed the GABAA response by initiating an Ca2+ dependent dephosphorylation process and the suppression is prevented by intracellular ATP-gamma-S or okadaic acid. Our study suggest that there interactions between the excitatory synaptic responses and the inhibitory synaptic responses may be effected with intracellular Ca2+ serving as a second messenger.