We used positron emission tomography with [15O]water and [18F]fluoro-2-deoxyglucose (FDG) to study the effect of naloxone on cerebral blood flow (CBF) and glucose metabolism (LCMRglc) in patients with complex partial seizures. There was no effect on glucose metabolism, but blood flow was reduced 7-12% 45-60 min after infusion of 1 mg/kg naloxone, as was the degree of lateral temporal CBF asymmetry in patients with > 10% baseline hypoperfusion. Endogenous opiates are involved in regulation of human CBF, and possibly in hypoperfusion in epileptic foci. Since [18F]FDG PET measures mean LCMRglc over the tracer uptake and scanning periods, it is inferior to [15O]H2O PET for detecting drug effects which may be time dependent.