Phenylketonuria (PKU) is a metabolic disorder which causes mental retardation when untreated. However, according to preliminary evidence generated by the Collaborative Study of Children Treated for Phenylketonuria, such cognitive damage can be prevented or ameliorated by the initiation of dietary therapy during the first month of life and monitored carefully during subsequent years. Approximately 150 PKU children have been studied since the inception of the Collaborative Project on October 1, 1967, and they now range in age from two to seven years. Having documented the value of treatment on their behalf, a subsequent question of great medical significance should now be answered: how long must dietary therapy be continued and what are the cognitive and physical consequences of its termination? The present application is addressed to that issue. It is hereby proposed that the 150 children be randomly assigned at six years of age to either a dietary continuation or discontinuation group. The two groups would then be evaluated according to a detailed schedule of assessment for three years, with comparisons of their status made regularly throughout the investigation. Systematic examination of intellectual, perceptual and academic skills would be made, in addition to assessments of growth, general health, biochemistry, nutrition, and psychosocial variables. The findings from this study are expected to have major applicability for the treatment of phenylketonuria in the foreseeable future.