1. 1. The agonist-induced accumulation of [3H]IP in the presence of lithium represents a sensitive method for studying a number of receptor-mediated events in brain.2. 2. In the presence of lithium, receptor-mediated [3H]IP3 formation in brain is difficult to demonstrate. It is possible that lithium itself may prevent the formation if IP3 and, thus, the presence of lithium in the incubation may account for such a discrepancy.3. 3. It is likely that the effects of lithium on the PI cascade are more complex then previously envisioned.4. 4. The recent identification of the inositol polyphosphates, myo-inositol 1,3,4-trisphosphate and myo-inositol 1,3,4,5-tetrakisphosphate, indicates that other inositol phosphates need to be considered in future studies of receptor-mediated PI metabolism.