In the present paper the effect of lithium on the level of cAMP in the rat striatum was studied. Incubation of the striatal slices in the presence of LiCl (1 mM) resulted in the significant decrease in the cAMP level stimulated by dopamine (via dopaminergic receptor), guanylyl-5-imidodiphosphate (GppNHp, via G protein) and forskolin (a direct activator of adenylate cyclase), without any effect on the basal level of cAMP. On the other hand, the effect of prolonged administration of LiCl (5 mEq/kg po) on the cAMP level in the striatal tissue was much more complicated and strongly depended not only on the stimulating factor used ex vivo (i.e. dopamine, GppNHp or forskolin) but also on the period of lithium administration (i.e. 1, 3, 7 or 21 days) and on the time after each of the above mentioned doses (i.e. 3 or 24 h). From the obtained results it can be concluded that initial inhibitory effect of LiCl on the cAMP level can be overcome upon the prolonged administration of the drug, by the adaptive changes which take place apparently at the level of catalytic unit of adenylate cyclase.