Phenylketonuria was experimentally induced in one group of pregnant rats by supplementing their diets with a-methylphenylalanine and phenylalanine on Days 10-21 of gestation. Control groups were either pair fed or ad-lib fed. Offspring of the drug-treated mothers were deficient on several measures of swimming development, active avoidance acquisition, and initiation of masculine sexual behavior. This experimental model of maternal PKU has been shown to exhibit fewer toxic effects than earlier models. The fact that the treatment induced enduring behavioral deficits, over and above deficits related to lower maternal food intake, suggests that this model is a useful one for studying the biochemical mechanisms of and treatment for maternal PKU.Phenylketonuria (PKU) is an inherited disease causing severe mental retardation and other manifestations of brain damage. Mental retardation not only is associated with classic or homozygous PKU, but is also found in most heterozygous infants of phenylketonuric mothers (Lenke & Levy, 1980). Since dietary treatment of children with classic PKU has resulted in an increased number of PKU females reaching childbearing age, there is a need for more information concerning the developmental processes affected by maternal, as well as classic, PKU.Biochemically, PKU is characterized by a deficit in the normal conversion of phenylalanine to tyrosine, which results in a surplus of phenylalanine and in other related biochemical changes. Earlier animal models of this disease employing phenylalanine in combination with parachloro-phenylalanine produced toxic side effects and death (Anderson, 1976;Copenhaver, Carver, & Schalock, 1974). A recent animal model of maternal PKU utilized increased dietary phenylalanine together with a-methylphenylalanine, which resulted in fewer toxic side effects than phenylalanine with para-chloro-phenylalanine (Brass, Isaacs, McHesney, & Greengard, 1982). This drug regimen resulted in a 5-10 fold increase in brain phenylalanine of treated fetuses, compared with that of controls. Since no single experimental model of PKU exactly replicates the biochemical environment of PKU, it would be advantageous to compare different models, each of which This research was submitted by Ann T. Hanulak in partial fulfillment of requirements for graduation from Calasanctius Preparatory School.