The purpose of the present study was to explore the brain regions involved in human episodic memory by correlating unilateral memory performance estimated by the intracarotid amobarbital test (IAT) and interictal cerebral metabolism measured by [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET). Using this method, regional alterations of cerebral metabolism associated with epilepsy pathophysiology are used to predict hemisphere-specific episodic memory function, hence, investigate the differential distribution of memory in each hemisphere. Sixty-two patients with unilateral temporal lobe epilepsy (35 left and 27 right) were studied using [18F]FDG-PET with complementary voxel-based statistical parametric mapping (SPM) and region-of-interest (ROI) methods of analysis. Positive regression was analyzed in SPM with a series of different thresholds (p = .001, .01 or .05) with a correction to 100 voxels. IAT memory performance in which left hemisphere was tested by right-sided injection of amobarbital correlated with [18F]FDG uptake in left lateral and medial temporal regions, and in the left ventrolateral frontal cortex. Right IAT memory performance correlated with [18F]FDG uptake in the right inferior parietal lobule, right dorsolateral frontal cortex, right precentral gyrus, and caudal portion of the right anterior cingulate cortex. ROI analysis corroborated these results. Analyses carried out separately in patients with left (n = 50) and nonleft (n = 12) dominance for language showed that in the nonleft dominant group, right IAT scores correlated with right fronto-temporal regions, whereas left total memory scores correlated with left lateral and medial temporal regions. The findings indicate that (i) episodic memory is subserved by more widespread cortical regions beyond the core mesiotemporal lobe memory structures; (ii) there are different networks functional in the two hemispheres; and (iii) areas involved in memory may be different between patients with left and nonleft dominance for language, particularly in the right hemisphere.