The cerebral distribution of 99mTc-labeled d, l, hexamethyl-propylene-amine-oxime (99mTc-HMPAO) as a function of rCBF and time was examined in rats and in man. The results of this study confirm that 99mTc-HMPAO is distributed in brain in proportion to rCBF. However, the rapid systemic breakdown of the tracer in blood results in considerable difficulties in the assessment of the arterial concentration of the parent compound; incomplete extraction of 99mTc-HMPAO from blood to brain and significant efflux from brain represent further limitations in the use of this tracer for quantification of rCFB. Despite these limitations 99mTc-HMPAO is of potential interest for a qualitative assessment of rCBF in specific clinical conditions.