Iodine-123-labeled N-isopropyl-p-iodoamphetamine (IMP) has been reported to be an excellent tracer for mapping cerebral blood flow with single-photon emission computed tomography (SPECT). Clinical interpretation of these SPECT images, however, requires further understanding of the kinetics of IMP in the human brain. In order to evaluate the kinetic behavior of IMP in normal and diseased areas, we measured flow and back-diffusion rates with serial dynamic SPECT scans following an intravenous bolus injection of IMP using a multi-detector SPECT scanner. Arterial input function was determined by octanol extracted radioactivity of serial arterial blood samples. Average values for influx rate (K1) and back-diffusion rate (k2) were 0.43 ml/g/min and 0.014 min-1 in the normal cerebral cortex, 0.43 and 0.013 in the basal ganglia, 0.28 and 0.012 in the white matter and 0.48 and 0.016 in the cerebellar hemisphere. The partition coefficient (K1/k2 ratio) was 32.4 ml/g in the cerebral cortex, 35.3 in the basal ganglia, 24.7 in the white matter and 30.4 in the cerebellum. The K1-to-k2 ratio in the infarcted and ischemic regions as well as in the tumor was smaller than that of the normal cortex. Accurate measurement of local cerebral blood flow (LCBF) based on the microsphere model was possible only on the early SPECT images, but a relative pattern of LCBF can be assessed with SPECT images obtained within 1 hr after injection except for tumors.