Lithium, with an atomic weight of 6.9, is the smallest of the alkali metals, yet this simple ion can exert a profound effect on both human behavior and early embryonic development. Manic-depressive psychosis, characterized by dramatic swings in mood, can be effectively controlled by maintaining a serum level of Li+ of~ 1 mM. Despite its therapeutic success, little is known about the way Li+ can modify neurotransmission within the central nervous system (CNS). Many of the proposed mechanisms have suggested an inhibitory effect on components of various neurotransmitter signaling pathways, such as cyclic AMP formation, cyclic GMP formation, G proteins, or inositol phosphate metabolism (Hallcher and Sherman, 1960; Berridge et al., 1962). Only the latter provides a plausible explanation of the Li+ conundrum, ie, the reason this ion