Rat superior cervical sympathetic ganglion was used to begin studying the regulation of molecular components of the synapse. Ganglionic postsynaptic densities (PSDs)exhibited a thin, disc-shaped profile electron microscopically, comparable to that described for brain. Moreover, the presumptive ganglionic PSD protein (PSDp) was phosphorylated in the presence of Ca2+ and calmodulin, bound 125I-labeled calmodulin, and exhibited a Mr of 51,000, all characteristic of the major PSD protein of brain. These initial studies indicated that ganglionic PSDp and the major PSD protein of brain are comparable, allowing us to study synaptic regulation in the well-defined superior cervical sympathetic ganglion. To obtain enough quantities of ganglionic PSDp, we used synaptic membrane fractions. During postnatal development, calmodulin binding to the ganglionic PSDp increased 411-fold per ganglion from birth to 60 days, whereas synaptic membrane protein increased only 4.5-fold. Consequently, different synaptic components apparently develop differently. Moreover, denervation of the superior cervical sympathetic ganglion in adult rats caused an 85% decrease in ganglionic PSDp-calmodulin binding, but denervation caused no change in synaptic membrane protein 2 weeks postoperatively. Our observations suggest that presynaptic innervation selectively regulates specific molecular components of the postsynaptic membrane structure.