The aim of this study was to evaluate the contribution of ionotropic glutamate receptors to kindled seizure-evoked somatostatin release in the hippocampus, using a microdialysis approach. Basal and amygdala stimulation-evoked somatostatin-like immunoreactivity (-LI) release was significantly greater in kindled compared to naive rats. In naive rats, neither hippocampal perfusion with the selective AMPA/kainate receptor antagonist GYKI 52466 nor with the selective NMDA receptor antagonist MK-801 affected behavior, EEG, or somatostatin-LI release. In kindled rats, GYKI 52466 was still devoid of any effect, while MK-801 significantly decreased stimulus-evoked (but not basal) somatostatin-LI efflux. MK-801 produced identical effects when injected i.p. This study provides the first direct evidence that kindled seizure-evoked somatostatin release in the hippocampus is partly NMDA receptor dependent.