The ability of the adenosine A1 receptor selective agonist, N6-cyclopentyladenosine, to modify basal accumulation of inositol phosphates in rat hippocampal slices, was investigated. Cyclopentyladenosine (10-300 nM) inhibited the basal accumulation of total [3H]inositol phosphates, with an EC50 of 10 nM and an Emax of 24%. This effect of cyclopentyladenosine was prevented by the adenosine A1 receptor selective antagonist, 1,3-dipropyl-8-cyclopentylxanthine (30 nM). Cyclopentyladenosine (100 nM) also inhibited histamine (300 μM)-stimulated accumulation of [3H]inositol phosphates, this effect being quantitatively similar to that observed on basal [3H]inositol phosphates accumulation. The results suggest that adenosine A1 receptor activation is able, per se, to inhibit the formation of phosphatidylinositol-derived second messengers in hippocampus.