Functional MRI (fMRI) was used to examine the relationship between processing of pleasant and unpleasant stimuli and activity in prefrontal cortex. Twenty volunteers identified the colors in which pleasant, neutral, and unpleasant words were printed. Pleasant words prompted more activity bilaterally in dorsolateral prefrontal cortex (DLPFC) than did unpleasant words. In addition, pleasant words prompted more activity in left than in right DLPFC. Response speed to pleasant words was correlated with DLPFC activity. These data directly link positive affect, enhanced performance, and prefrontal activity, providing some of the first fMRI evidence supporting models of emotional valence and frontal brain asymmetry based on electroencephalography (EEG).