A number of theories on the cellular basis of learning and memory propose that long-term changes in synaptic strength are encoded by changes in the properties of dendritic spines. Such theories imply that individual spines retain their identity over time. Using a new technique for fluorescent labelling of synaptic structures together with confocal microscopy, we have found that the appearance of individual spines on viable cells remains unchanged over observations periods of up to 5 hours. Even in slices exposed to kainic acid at concentrations that abolished synaptic transmission, groups of spines remained identifiable on cells clearly damaged by the toxin. The robust persistence of individual spines demonstrated here establishes an essential prerequisite for their potential role as mnemonic elements.