Abstract We performed positron emission tomography using carbonyl-11 C WAY-100635, a serotonin 1A (5-HT1A ) receptor antagonist, in 13 patients with temporal lobe epilepsy (TLE) and in 13 controls. 5-HT1A receptor distribution mapping allowed correct lateralization of the epileptogenic temporal lobe in all patients. 5-HT1A receptor binding potential (BPND ) was significantly reduced in almost all temporal regions of the epileptogenic lobe. Compared with controls, the patients had significantly decreased BPND values in the hippocampus, parahippocampal gyrus, and amygdala. The asymmetry index (AI), which characterizes the interhemispheric asymmetry in BPND , was significantly higher in patients than in controls in most regions. Depression scores were not significantly correlated with BPND or AI values. Our data provide further evidence of functional changes in the serotonergic system in TLE. Molecular imaging of the 5-HT1A receptor may help to define the in vivo neurochemistry of TLE, and may provide a valuable tool in the noninvasive presurgical assessment of patients with medically refractory TLE.