Rat superior cervical ganglia, when stimulated in lithium-containing bathing solution, show decreasing action potentials with increasing lithium concentrations. When 70% of the sodium is replaced by lithium there is an irreversible loss of the action potential. This is not reversed by returning the ganglion to normal bathing solution, with or without stimulation. The decrease in ganglionic transmission is similar when only the pre-ganglionic fibers or the ganglionic body and the post-ganglionic fibers are exposed to lithium-containing bathing solution (compartmentalized cell). The experiments suggest that lithium has two effects; the usual depression of the action potential and the more sensitive action on the synaptical transmission.