To date, there has been no satisfactory explanation for the observation that interictal uptake of the glucose analog [18F]fluorodeoxyglucose (FDG) is consistently reduced in the temporal lobe ipsilateral to the seizure focus in patients with temporal lobe epilepsy. We examined the hypothesis that regional differences in tracer uptake in temporal lobe epilepsy reflect regional differences in the lumped constant (lambda). METHODS: In 9 control subjects and 10 patients with temporal lobe epilepsy, we obtained regional estimates of lambda by expressing lambda in terms of transfer coefficients for FDG and parameters which are likely to remain constant throughout both the brain and under different functional states. RESULTS: In the patients, lambda was lower in the temporal lobe ipsilateral to the epileptic focus (0.53 +/- 0.06; p < 0.005) than in the contralateral temporal lobe (0.56 +/- 0.06). Interside differences in lambda were highly correlated with asymmetry in tracer uptake. Furthermore, the use of regional estimates of lambda reduced the asymmetry in estimated rCMRglc in patients with temporal lobe epilepsy but not in controls. CONCLUSION: In these patients, a change in tracer uptake may not indicate a change in glucose consumption of corresponding magnitude, raising the possibility that in at least some patients with temporal lobe epilepsy, the term hypometabolism does not accurately describe reductions in tracer uptake.