The efficacy of lithium carbonate (Li) in preventing ischemic brain injury was evaluated in 36 dogs in a vegetative state. The dogs were subjected to 18 minutes of complete global brain ischemia and diveded into the following three groups ; control group (n=12), L-Ⅰ group (n=12), and L-Ⅱ group (n=12). In the L-Ⅰand L-Ⅱgroups, dogs were administered Li (10mg/kg) immediately after the end of ischemia (post-treatment). Only in the L-Ⅱ group, dogs were administered Li (100mg/kg) orally one day before the ischemic insult (pre-treatment). In each group, nuerologic outcome was evaluated for seven days after ischemia, and morphological changes in hippocampal CA1 pyramidal cells, small to medium-sized striatal neurons and cerebellar Purkinje cells were evaluated at day seven. In the L-Ⅱ group, neutrologic outcome was significantly better than that in the control group, and morphological improvement was recognized. Pre-treatment with Li might improve both neurologic and morphologic outcomes due to powerful inhibition of the stimulated phosphoinositide turnover during ishchemia. These fingings suggest that the stimulated phosphoinositide turnover during and immediately after ischemia might play an important role in brain injury induced by 18 minutes of complete global brain ischemia.