Lithium pretreatment in rats potentiates the epileptogenic effects of pilocarpine and other cholinergic agonists. In order to determine if this effect of lithium could be reversed by myo-inositol, rats were pretreated with intracerebroventricular (ICV) injections of myo-inositol, artificial CSF or L-chiro-inositol. Lithium chloride, 3 meq/kg was administered intraperitoneally 20-24 h prior to the subcutaneous injection of pilocarpine, 20 or 30 mg/kg. In both experiments, myo-inositol significantly prolonged the latency to the appearance of clonic seizures and lowered the pilocarpine seizure score. myo-Inositol prevented the development of clonic seizures in 50% of the rats receiving pilocarpine, 20 mg/kg. The levels of cortical myo-inositol in rats injected with myo-inositol were approximately double those of the CSF and L-chiro-inositol groups.