PSD-95, a specialized scaffold protein with multiple protein interaction domains, forms the backbone of an extensive postsynaptic protein complex that organizes receptors and signal transduction molecules at the synaptic contact zone. Large, detergent-insoluble PSD-95-based postsynaptic complexes can be affinity-purified from conventional postsynaptic density (PSD) fractions using magnetic beads coated with a PSD-95 antibody. In the present study purified PSD-95 complexes were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). A semi-quantitative measure of the relative abundances of proteins in the purified PSD-95 complexes and the parent PSD fraction was estimated based on the cumulative ion current intensities of corresponding peptides. The affinity-purified preparation was largely depleted of presynaptic proteins, spectrin, intermediate filaments and other contaminants prominent in the parent PSD fraction. We identified 525 of the proteins previously reported in parent PSD fractions, but only 288 of these were detected after affinity purification. We discuss 26 proteins that are major components in the PSD-95 complex based upon abundance ranking and affinity co-purification with PSD-95. This subset represents a minimal list of constituent proteins of the PSD-95 complex and includes, in addition to the specialized scaffolds and NMDA receptors, an abundance of AMPA receptors, small G protein regulators, cell adhesion molecules and hypothetical proteins. The identification of two Arf regulators, BRAG1 and BRAG2b as co-purifying components of the complex implies pivotal functions in spine plasticity such as the re-organization of the actin cytoskeleton and insertion and retrieval of proteins to and from the plasma membrane. Another co-purifying protein, the hypothetical protein (Q8BZM2) with two SAM domains, may represent a novel structural core element of the PSD.