The effects of a very short ischemic insult on hilar somatostatin (SS) neurons were investigated in the gerbil hippocampus by means of immunocytochemistry and in situ hybridization histochemistry. A selective and significant loss of 40% of hilar SS neurons took place after 1 day, and a 60% loss after 7 days following 2 min of ischemia, while no SS neurons were lost during recirculation after 1 min of ischemia. Repeated 2-min periods of ischemia, which induced ischemic tolerance by vulnerable CA1 neurons, caused almost complete loss of hilar SS neurons. This study clearly demonstrates that hilar SS neurons are more vulnerable to ischemic insult than CA1 pyramidal neurons. Ischemic tolerance may be induced during the progressive loss of SS neurons in the hilus by changes in their synaptic connections to CA1 pyramidal neurons.