A well established in vitro blood-brain barrier (BBB) model, consisting of bovine cerebrovascular endothelial monolayers from primary cultures, was used to study the transport profile of vasopressin and its fragments across the BBB and to assess the metabolic properties of the BBB for the behaviorally active vasopressin fragment arginine vasopressin (AVP)1-8 (desglycinamide-AVP). All vasopressin fragments crossed the in vitro BBB to a measurable extent. Endothelial permeabilities were (in 10(-3) cm/min): AVP1-6, 3.0 +/- 0.2; AVP1-7, 4.6 +/- 0.4; AVP1-8, 2.0 +/- 0.5 and AVP1-9, 2.4 +/- 0.4. A significant effect of molecular size on endothelial permeability was seen. Transport rate of AVP1-8, expressed as BBB-clearance, was not affected by luminal concentration change and proved to be symmetrical. These findings suggest that, in the concentration range studied, vasopressin-like peptides can cross the BBB mainly by paracellular transport and that no relevant carrier mediation is involved. AVP1-8 was metabolized slowly (half-life, 6.5 hr) by a 60 cm2 confluent monolayer to AVP1-7, which was not broken down further, suggesting that carboxypeptidases are responsible for AVP1-8 metabolism in the BBB.