THE possibility that postsynaptic spines on neuronal dendrites are discrete biochemical compartments for Ca2+-activated processes involved in synaptic plasticity 1-6 is a widely proposed concept that has eluded experimental demonstration. Using microfluorometry on CA3 neurons in hippocampal slices, we show here that with weak presynaptic stimulation of associative/commissural fibres, Ca2+ accumulates in single postsynaptic spines but not in the parent dendrite. Stronger stimulation also promotes changes in dendrites. The NMDA-receptor antagonist AP-5 blocks changes in Ca2+ in spines. Sustained steep Ca2+ gradients between single spines and the parent dendrite, often lasting several minutes, develop with repeated stimulation. The observed compartmentalization allows for the specificity 7,8, cooperativity 9 and associativity 10-14 displayed by memory models such as long-term potentiation.