Intracellular calcium levels were measured by ratio imaging of Fura-2-injected CA1 pyramidal neurons during repetitive electrical stimulation of the Schaffer collaterals in rat hippocampal slices. Baseline intracellular calcium levels of 102 nM increased to 190 nM during a 3-s stimulus train of 5 Hz. Bicuculline (20 microM) significantly enhanced this stimulus-dependent rise in intracellular calcium, while the baseline calcium levels remained unchanged. Concomitantly performed extra- and intracellular electrophysiological recordings indicate that the increased calcium response in the presence of bicuculline is linked to a prolongation of the excitatory postsynaptic potential and the induction of multiple action potentials. The bicuculline-induced increased calcium response could have long-term implications for cell function and eventually lead to cell degeneration.