- A previous open study suggested that oral inositol 3 g/day ameliorates lithium-induced polyuria–polydipsia as rated subjectively by patients. We designed a double-blind crossover study of 6 g/day oral inositol versus placebo, each given for 2 weeks, in seven patients. Inositol did not reverse lithium-induced polyuria, as measured by 24 h urine volume and urine specific gravity. However, subjects' subjective report of symptomatology was significantly improved on inositol as compared to placebo, possibly due to alleviation of polydipsia. Inositol was previously shown to reverse lithium-induced polydipsia in rats. Such a phenomenon may be mediated by either a central or a peripheral mechanism. In order to study such suggested mechanisms, we injected daily inositol or artificial CSF i.c.v. to rats exhibiting lithium-induced polydipsia. Inositol i.c.v. reversed lithium-induced polydipsia, but kidney inositol levels in Li-treated rats were not different from controls. These findings suggest that inositol may alleviate symptoms of lithium-induced polydipsia via a central effect, but has no direct effect on lithium-induced polyuria. © 1997 John Wiley & Sons, Ltd.