- Lithium (Li) is an effective drug for prophylaxis and treatment of major affective disorders. It is teratogenic both to animals and human beings. Depletion of inositol is associated both with lithium side effects and teratogenesis. There is no direct evidence showing that in humans Li-teratogenesis is associated with the phosphoinositol (PI) cycle. It is conceivable that the teratogenic effect of Li in humans is also associated with inositol depletion and therefore is amenable to inositol supplementation. To test the hypothesis that oral inositol may cross the placental barrier and may be useful as a protective supplement to lithium therapy during pregnancy, we studied the effect of 2.5% inositol in drinking water on embryonic inositol levels in rats. There was no effect on fetal inositol concentration. However, weight of embryos of mothers receiving inositol was significantly higher. These data do not support the concept that inositol supplementation may be useful in preventing human Li-induced teratogenesis.