Extracellular population responses are largely preferred for the study of long-term potentiation (LTP). The effect of Mg2+-free medium on changes in activity and plasticity of Schaffer collateral-CA1 pyramidal cell synapses was examined. Hippcampal slices from cysteamine-treated (200 mg/kg, s.c.) and saline-injected (1 ml/kg, s.c.) albino rats were perfused with ACSF. Population spikes (PS) were recorded in CA1 cell body layer following Schaffer-collateral stimulation. The results showed that Mg2+-free medium enhances the amplitude of population spike (PSA). At 60 min following Mg2+-free medium washout, an increase in PSA was observed at both groups. The extent of LTP of PSA was significantly lower in cysteamine-treated rats in comparison with saline-injected ones. It is concluded that the effect of cysteamine (a somatostatin depletor) can entail lasting modifications in susceptibility of hippocampal CA1 for synaptic plasticity induced by Mg2+-free medium. The relevancy of the results to the facilitatory role of endogenous somatostatin in the function of Schaffer collateral-CA1 pyramidal cell synapses should also be considered.