Using positron emission tomography (PET), we measured the regional cerebral blood flow (rCBF) in five normal human subjects after intravenous injection of carbon-11 labeled (R)nicotine. The rCBF of the same subjects was measured by PET using the C15O2 inhalation steady-state method. The distribution of 11C activity in the brain after injection of 11C-(R)nicotine was almost equivalent to the CBF image obtained with the C15O2 inhalation stead-state method. The kinetics of 11C-(R)nicotine in the brain was analysed using a two-compartment model consisting of vascular and brain tissue compartments. The rCBF values obtained with 11C-(R)nicotine were higher than with C15O2 gas. The relatively long fixed distribution of 11C-(R)nicotine with a short uptake period allows stimulation studies by measurement of CBF to be performed with better photon flux and a longer imaging time than are possible with H215O.