Myo-inositol is an important precursor in cellular second-messenger synthesis. It has been reported to be reduced in the cerebrospinal fluid of depressed patients and to reverse a specific effect of Li on rat behavior when given intracerebroventricularly (i.c.v.). However, myo-inositol enters the brain poorly when given peripherally, and its effects on normal rat brain have not been well studied. A series of experiments examined the effect of intraperitoneal inositol in high doses on locomotor activity, on amphetamine-induced hyperactivity, on apomorphine-induced stereotyped behavior, and on pilocarpine-induced behaviors in rats. In addition, the behavioral effect of i.c.v. inositol was compared to that of a control stereoisomer in untreated and lithium-treated rats. Few effects of peripheral myo-inositol were found in these models. However, peripheral inositol in high doses given to rats exhibiting Li-pilocarpine seizures showed that i.p. inositol could prevent these behaviors, confirming that peripheral inositol may have antidepressant potential in appropriate models.