In recent neuroimaging studies, various tasks have been used to examine prefrontal cortex involvement in semantic retrieval and selection. One such task, picture naming, has yielded inconsistent results across studies. One potential explanation for this inconsistency is that the magnitude of prefrontal activity during picture naming depends on the extent to which a given picture evokes a single reliable meaning. To test this hypothesis, fMRI activity in the prefrontal cortex was measured while subjects named pictures with either high or low name agreement. In Experiment 1, subjects named black-and-white line drawings, either covertly or overtly. Across both modalities, we found more left inferior frontal gyrus (LIFG) activity when the subjects named low-agreement pictures than when they named high-agreement pictures. No significant difference in head movement was detected between the two modalities. In Experiment 2, we replicated the effect of name agreement on LIFG activity during picture naming, using black-and-white photographs. These results provide further support for the idea that the LIFG mediates selection among competing alternatives and suggest a means for understanding the naming deficits observed in nonfluent aphasia.