The authors used functional magnetic resonance imaging (fMRI) to investigate neural activation during a semantic-classification/object-recognition task in 13 persons with Down syndrome and 12 typically developing control participants (age range = 12-26 years). A comparison between groups suggested atypical patterns of brain activation for the individuals with Down syndrome. Correlation analyses between an index of visual spatial ability and brain activation depicted a positive relationship between (a) this index and brain activation in regions of the occipital and parietal lobes for the typically developing individuals and (b) the middle and dorsal frontal gyri in the individuals with Down syndrome. These findings supported the authors' hypothesis that persons with Down syndrome demonstrate atypical neural activation compared with typically developing individuals matched for chronological age.