PACAP is a member of the secretin/glucagon/VIP family of peptides and demonstrates neurotrophic and neuroprotective effects at very low concentrations. We have previously shown that PACAP crosses the BBB to a modest degree by way of a saturable transport system. PACAP is transported across the BBB as an intact peptide to enter the parenchymal space of the brain. We tested the possibility that this modest rate of transport would be sufficient to produce the low levels of PACAP needed in the brain to exert a neuroprotective effect against ischemia. We found that PACAP given intravenously could indeed prevent the death of CA1 hippocampal neurons, even if the administration of PACAP was delayed for 24 h after the ischemic event. We suggest that iv PACAP could be neuroprotective after stroke, cardiac arrest, and hypotensive episodes.