The signal transduction system of the vasopressin receptor in cerebral microvessels is not known but appears not to be adenylate cyclase/cyclic AMP. We determined the effect of arginine vasopressin (AVP) on the intracellular free calcium concentration [Ca2+]i in endothelial cells of isolated hippocampal microvessels of rats, using the fura-2 fluorescence technique. AVP administration caused a rapid and transient rise of cytosolic free calcium which was absent after extracellular calcium was removed, and could be blocked with the vasopressin V1 receptor antagonist, d(CH2)5Tyr-(Me)AVP. The vasopressin V2 receptor agonist, 1-deamino-8,D-AVP, on the contrary, failed to affect the intracellular free calcium level, and was unable to inhibit the AVP-induced rise of [Ca2+]i in the preparation. Our results, therefore, demonstrate the presence of a calcium-signalling, i.e. V1 vasopressin receptor at the blood-brain barrier in the hippocampus of the rat.