The prefrontal cortex has been implicated in the mediation of executive processes that facilitate learning and memory. The authors hypothesized that children with prefrontal dysfunction related to phenylketonuria (PKU) would experience deficits in learning and memory because of impaired strategy use. They evaluated 23 children with PKU and 23 controls by using the California Verbal Learning Test-Children's Version (CVLT-C). General executive abilities were tested using the Stroop Color and Word Test, the Wisconsin Card Sorting Test, and phonemic and category fluency. Children with PKU, especially older children, showed poorer learning across trials and less use of semantic clustering on the CVLT-C but intact retention of previously encoded information. With the exception of phonemic fluency, deficits were not observed in general executive control. Results are discussed within the context of abnormalities in the prefrontal cortex and white matter of the brain.