Steady-state arterial spin-tagging MRI approaches were used to quantitate regional cerebral blood flow increases in prefrontal cortex during a working memory ("two-back") task in six normal subjects. Statistically significant increases in cerebral blood flow in prefrontal cortex were observed in all six subjects: the average increase in cerebral blood flow in activated prefrontal cortex regions was 22 +/- 5 cc/100 g/min (23 +/- 7%). The results demonstrate that spin-tagging approaches can be used to follow focal activation in prefrontal cortex during cognitive tasks.