The conditions under which pretreatment with a calcium salt may prevent the action of reserpine on brain noradrenaline stores in the rat were investigated. The results show that only after subcutaneous administration of reserpine in the same site as a previous CaCl2 injection, was the action of reserpine prevented and reduced levels of this drug were found in the brain. Conversely, the depletion of encephalic noradrenaline following reserpine, as well as the reserpine brain concentration, were not affected by subcutaneously administered calcium chloride, when reserpine was administered either intravenously, or subcutaneously in a site different from that selected for pretreatment with the calcium salt. In essence calcium chloride, a well known irritant, acts accordingly at the site of subcutaneous administration, thus limiting by a non specific mechanism the absorption of reserpine. Under similar conditions, in fact, the absorption of a different drug, i.e. harmaline, was likewise altered. In view of these findings the significance of some studies on calcium-reserpine interaction appearing in the literature requires a reappraisal.