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Efficient memory functions are important to the development of cognitive and functional skills, allowing individuals to manipulate and store information. Theories of memory have suggested the presence of domain-specific (i.e. verbal and spatial) and general processing mechanisms across memory domains, including memory functions dependent on the prefrontal cortex (PFC) and the hippocampus. Comparison of individuals who have syndromes associated with striking contrasts in skills on verbal and spatial tasks [e.g. Down syndrome (DS) and Williams syndrome (WS)] allows us to test whether or not these dissociations may extend across cognitive domains, including PFC and hippocampal memory processes.The profile of memory function, including immediate memory (IM), working memory (WM) and associative memory (AM), was examined in a sample of adolescents and young adults with DS (n = 27) or WS (n = 28), from which closely CA- and IQ-matched samples of individuals with DS (n = 18) or WS (n = 18) were generated. Relations between memory functions and IQ and adaptive behaviour were also assessed in the larger sample.Comparisons of the two matched groups indicated significant differences in verbal IM (DS < WS), spatial IM (DS > WS) and spatial and verbal AM (DS > WS), but no between-syndrome differences in WM. For individuals with DS, verbal IM was the most related to variation in IQ, and spatial AM related to adaptive behaviour. The pattern was clearly different for individuals with WS. Verbal and spatial AM were the most related to variation in IQ, and verbal WM related to adaptive behaviour.These results suggest that individuals with these two syndromes have very different patterns of relative strengths and weaknesses on memory measures, which do not fully mirror verbal and spatial dissociations. Furthermore, different patterns of memory dysfunction relate to outcome in individuals with each syndrome.