We investigated the relationship between somatostatin-like immunoreactivity (SSLI) and interictal spikes (IIS) in human temporal lobe epileptic tissue. IIS counted manually from depth electrode recordings obtained preoperatively were expressed as spike frequency in anterior, middle, and posterior portions of hippocampus. SSLI was determined by radioimmunoassay (RIA). An inverse relationship between SSLI in the entorhinal cortex (EC) and IIS frequency in hippocampus was present (r = -0.55, p = 0.06). No correlation between IIS and SSLI in CA4, CA3, CA1, or the dentate was evident. This finding suggests a role of the EC in generation, regulation, or expression of interictal paroxysmal electrical activity in temporal lobe epilepsy (TLE), for which somatostatin may be a marker.