During a conditioning stimulus, the influx of Ca2+ into neurons appears to be crucial for the induction of long-term potentiation at CA1 hippocampal synapses. We report here that extracellular Ca2+ is also required for full production of long-term potentiation during a critical period following the conditioning stimulus. In control slices, removal of extracellular Ca2+ (0 mM Ca2+/10 mM Mg2+) for 15 min eliminated synaptic transmission. Following reintroduction of normal extracellular solution, synaptic responses recovered fully within 15 min. However, removal of extracellular Ca2+ 15-30 min after theta burst stimulation significantly decreased the magnitude of long-term potentiation. A time window seems to exist for this effect, since either earlier or later Ca2+ removal was less effective. The effect of the 0 mM Ca2+/10 mM Mg2+ solution was observed in the absence of afferent stimulation, suggesting that evoked synaptic activity is not required. Perfusion with an extracellular solution containing Cd2+ (40 microM), a broad spectrum inhibitor of voltage-dependent Ca2+ channels, or a low concentration (50 microM) of Ni2+, which preferentially blocks T-type, low-voltage-activated Ca2+ channels, also caused a significant decrease in potentiation, whereas an inhibitor of L-type, high voltage-activated Ca2+ channel, nifedipine (20 microM), had no effect. These results suggest that the presence of extracellular Ca2+ during a specific period after high-frequency synaptic activity is necessary for the maintenance of long-term potentiation, and that voltage-gated Ca2+ channels play a role in the stabilization of synaptic plasticity.