Language impairments are a characteristic feature of autism and related autism spectrum disorders (ASDs). Autism is also highly heritable and one of the most promising candidate genes implicated in its pathogenesis is contactin-associated protein-like 2 (CNTNAP2), a gene also associated with language impairment. In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66). Against a background of normal performance and lack of behavioral abnormalities, healthy individuals with the putative risk allele versus those without demonstrated significant increases in activation in the right inferior frontal gyrus (Broca's area homologue) and right lateral temporal cortex. These findings demonstrate that risk associated variation in the CNTNAP2 gene impacts on brain activation in healthy non-autistic individuals during a language processing task providing evidence of the effect of genetic variation in CNTNAP2 on a core feature of ASDs. © 2011 Wiley Periodicals, Inc.