In order to test the feasibility of returning older children with classical phenylketonuria (PKU) to therapeutically and nutritionally adequate phenylalanine-restricted diets after 8 to 13 years of unrestricted diets, 7 adolescents (13 to 19 years old) of normal or near-normal intelligence with classical PKU were returned to phenylalanine-limited diets for periods of 8 to 10 weeks. During a 4- to 5-week period when the phenylalanine-restricted diet was supplemented with added L-phenylalanine to mimic pretreatment conditions, plasma phenylalanine levels were 1,327 +/- 282 microM on total phenylalanine intakes of 2,794 +/- 248 mg/day (55.3 +/- 11.5 mg/kg/day). During a similar period of dietary phenylalanine restriction, plasma phenylalanine levels were successfully maintained at 713 +/- 266 microM on dietary intakes of 655 +/- 210 mg/day (12.6 +/- 4.3 mg/kg/day). On the basis of 3-day diet records, the intakes of total protein, energy, calcium, phosphorus, iron, vitamins D, E, and A, ascorbic acid, thiamin, riboflavin, niacin, folacin, and vitamin B-12 over the entire 8- to 10-week study period were adequate by the standards of the Recommended Nutrient Intakes (RNI) for Canada, where the study was undertaken. Intakes of magnesium and zinc were significantly lower than the RNI. Although the return to nutritionally and therapeutically adequate dietary phenylalanine restriction was judged to be successful in each case, the amount and intensity of re-education and reinforcement required to maintain compliance was much greater than anticipated.