Synaptic plasticity is associated with morphological changes in dendritic spines. The actin-based cytoskeleton plays a key role in regulating spine structure, and actin reorganization in spines is critical for the maintenance of long term potentiation. To test the hypothesis that a stable pool of F-actin rests in the spine "core," while a dynamic pool lies peripherally in its "shell," we performed immunoelectron microscopy in the stratum radiatum of rat hippocampus to elucidate the subcellular distribution of cofilin, an actin-depolymerizing protein that mediates reorganization of the actin cytoskeleton. We provide direct evidence that cofilin in spines avoids the core, and instead concentrates in the shell and within the postsynaptic density. These data suggest that cofilin may link synaptic plasticity to the actin remodeling that underlies changes in spine morphology.