Histological and immunohistochemical techniques were used to investigate the long-term structural changes that occur in the rat hippocampal formation following the induction of transient forebrain ischemia. Histological analysis showed that after 6-12 months cell loss was still largely restricted to the CA1 region but within this region degeneration was progressive and culminated in a severe shrinkage of the stratum oriens and stratum radiatum. Using the immunohistochemical markers calbindin-D28K and parvalbumin, we were able to demonstrate some of the structural changes that reflect this shrinkage. Calbindin immunohistochemistry clearly illustrated that the shrinkage was primarily due to the loss of the pyramidal neurons and the framework normally provided by their long apical dendrites. Parvalbumin immunostaining demonstrated that although a few GABAergic interneurons survived the insult, their terminal network was reduced greatly and the dendrites which normally extended the length of the stratum radiatum were retracted. Additionally, the normally dense band of parvalbumin immunoreactivity in the stratum lacunosum-moleculare, thought to be indicative of a fiber bundle travelling through the CA1 region, was almost completely depleted. These data illustrate that the primary damage observed in the CA1 region following cerebral ischemia is not static but progressive and may thus have important functional implications.