The biochemical, morphological and structural properties of rat postsynaptic densities (PSDs) isolated under conditions where disulfide bond formation was allowed or curtailed were studied here. Biochemical analyses revealed that the isolated PSDs were composed by a similar set of proteins regardless of the differences in their isolation processes. The PSDs isolated under the conditions where disulfide bond formation was curtailed were more easily dissociated by treatments with urea, guanidine hydrochloride and deoxycholate than the PSDs isolated under conditions where disulfide bond formation was allowed. Consistently, the structure of the PSDs isolated under the former condition appeared to be more fragmented than those isolated under the latter condition, as revealed by electron microscopy. The results indicate that the disulfide bonds formed during the isolation process significantly tighten the PSD structure and further suggest that the PSD in vivo is a protein aggregate whose constituent proteins be held together primarily by non-covalent interactions.