The calcium-binding proteins, parvalbumin (PV) and calbindin (CaBP), were used as immunocytochemical markers for two different interneuron populations in the rat hippocampus shortly after transient cerebral ischemia. Besides in interneurons, CaBP immunoreactivity (-i) is located in hippocampal CA1 pyramidal cells and dentate granule cells. Shortly after ischemia, the PV-i and CaBP-i were unchanged but, around the 4th postischemic day, PV-i disappeared from somata and fibers located in CA1, CA3c, and the dentate hilus. Terminal PV-i was unchanged. Within days, the PV-i gradually reappeared, first in somata and then in fibers. The transient loss of PV-i was, on a time scale, closely accompanied by a permanent loss of CaBP-i in CA1 pyramidal cells. CaBP-i in interneurons was unchanged. In order to examine the effect of an increased intracellular calcium concentration on the PV-i and CaBP-i, the calcium ionophore A23187 was stereotaxically injected into CA1. In rats killed 30 min later and processed for PV-i and CaBP-i, both PV-i and CaBP-i had disappeared around the A23187 injection sites. Based on this observation and the changes observed after ischemia, it is suggested that the hippocampal PV-i interneurons suffer from a delayed and reversible calcium accumulation in the days after ischemia. Concomitantly, there could be a decreased synthesis or increased destruction of PV after ischemia.