The general aim of our research is to understand the brain mechanisms that underlie language and cognition. In this paper, we present a new line of investigation which attempts to forge links between a specific neurodevelopmental disorder, a specific neuropsychological profile, and abnormal brain organization. We report on a dissociation between language and cognitive functions in Williams syndrome adolescents, in contrast to age- and IQ-matched Down syndrome adolescents. The Williams syndrome individuals exhibit an unusual fractionation of higher cortical functioning, with marked cognitive deficits, but selective sparing of syntax. Differences in spatial cognitive abilities in the 2 groups are investigated, showing peaks and valleys of abilities specific to Williams syndrome individuals. These neurobehavioral profiles are explored in light of new evidence regarding neurologic and neuroanatomical differences between the 2 matched groups of adolescents. Results from these combined studies should help clarify the neural systems that mediate language and cognitive functions.