Both the medial temporal lobe and dorsolateral prefrontal cortex have been implicated in autism. In the present study, performance on two neuropsychological tasks--one tapping the medial temporal lobe and related limbic structures, and another tapping the dorsolateral prefrontal cortex--was examined in relation to performance on tasks assessing autistic symptoms in young children with autism, and developmentally matched groups of children with Down syndrome or typical development. Autistic symptoms included orienting to social stimuli, immediate and deferred motor imitation, shared attention, responses to emotional stimuli, and symbolic play. Compared with children with Down syndrome and typically developing children, children with autism performed significantly worse on both the medial temporal lobe and dorsolateral prefrontal tasks, and on tasks assessing symptoms domains. For children with autism, the severity of autistic symptoms was strongly and consistently correlated with performance on the medial temporal lobe task, but not the dorsolateral prefrontal task. The hypothesis that autism is related to dysfunction of the medial temporal lobe and related limbic structures, such as the orbital prefrontal cortex, is discussed.