We studied the radioisotope iodine-123-iodoamphetamine ([123I]IMP) and its performance in single-photon emission computed tomographic (SPECT) studies of cerebral blood flow (CBF). In seven normal volunteers, IMP/SPECT CBF measurements were calculated using a two-compartment model and were compared with the results of CBF measurements utilizing (O15)-H2O and positron emission tomography (PET). Calculated mean PET CBF was 57.6 ml/100 g/min while the SPECT CBF value was 47.3 ml/100 g/min. The response of IMP/SPECT CBF to alterations in arterial PaCO2 was studied in hypo-, eu- and hypercarbic subjects. SPECT CBF values showed a reactivity of 1.03 ml/100 g/min per mmHg PaCO2 change. These results show that the IMP/SPECT CBF technique may be used for quantitative imaging of CBF in man. They provide further support for IMP as a CBF tracer.