The aim of this study was to clarify the controversy about the effects of indomethacin on the coupling of cerebral blood flow (CBF) to cerebral oxygen metabolism (CMRO2). CBF, blood volume (CBV), oxygen extraction fraction (OEF) and CMRO2 were measured by positron emission tomography (PET) in five anaesthetized baboons before and during an i.v. administration of indomethacin (bolus 20 mg/kg followed by perfusion 10 mg/kg.h). Administration of indomethacin resulted in a marked and homogenous decrease of CBF in every region analysed (-28% to -40%) and a moderate reduction in CBV (-8% to -16%). In contrast, CMRO2 displayed a small increase in thalamus and pons (+10% and +13%, respectively). OEF increased greatly in all structures studied (+59% to +96%). These findings show that the potent cerebrovascular effects of indomethacin are not related to a decrease in CMRO2 as measured through the use of PET.