Somatostatin (SS)- and cholecystokinin (CCK)-immunopositive cell somata in the rat hippocampus were quantitated at day 1, 2, 3 and 4 after cerebral ischemia. A significant (P less than 0.01) 60%-80% loss of hilar and CA-3c SS neurons took place. No CCK neurons were lost. Damage to SS neurons was significant on the second postischemic day and preceded the delayed loss of CA-1 neurons. We speculate that loss of SS neurons, which presumably innervate the inhibitory GABAergic (gamma-aminobutyric acid) interneurons, may induce hyperactivity stimulating the Ca-1 neurons to death.