The binding of neurotransmitters and certain drugs to neuroreceptors in the brain is considered to modify cognition and behavior by activating certain receptor-coupled effector enzymes and initiating signal transduction cascades. One of these effector enzymes is phospholipase A2 (PLA2), which when activated will release arachidonic acid (AA) from phospholipids and initiate the AA cascade (Fitzpatrick and Soberman, 2001). AA and its eicosanoid metabolites have multiple biological actions. We have developed an imaging method to quantify and localize brain signal transduction involving PLA2 and AA in unanesthetized rats and monkeys, using quantitative autoradiography or positron emission tomography (PET), and radiolabeled AA. The aim of this protocol is to extend this method to humans with PET, when brain imaging AA signaling in two experimental conditions (dark and visual flash stimulation at a frequency of 3 Hz or 8Hz) in the same subject in the same PET session. Radioactive [1-11C]AA will be injected intravenously in each condition, and PET will be used to measure its incorporation coefficient k* in individual brain regions. Animal studies and modeling have shown that the incorporation coefficient is proportion to PLA2 activation and the release of AA from brain phospholipids (Rapoport, 2003). In addition, [15O]H20 will be injected in each condition to measure regional cerebral blood flow (rCBF). Based on our prior studies in human subjects of rCBF during visual activation by flashing lights at different frequencies (Mentis et al., 1997; Mentis et al., 1998; Mentis et al., 1996), we hypothesize that statistically significant increments in rCBF and [11C]AA incorporation into brain will be increased during visual activation compared with the dark (unactivated) condition. These increments should be evident in primary visual cortex, association visual cortex, thalamus, and frontal cortex. If our hypothesis proves correct and our method to measure [11C]AA incorporation both during stimulation and in the dark proves feasible in the same subject in the PET session, we believe that the method could be applied generally in humans to examine brain PLA2-related signal transduction during physiological or pharmacological activation and in healthy aging (Giovacchini et al., In press) and disease, particularly Parkinson and Alzheimer disease (Hayakawa et al., 2001; Nariai et al., 1991).