A deficit of alpha-aspartyl-phenylalanine (alpha-Asp-Phe) hydrolase activity has been suggested as a cause of possible adverse effects of aspartame ingestion. Twenty-five normal preschool children and 23 school-age children described by their parents as sensitive to sugar were fed diets high in sucrose, aspartame, or saccharin for three successive 3-wk periods. Blood samples were obtained at baseline (fasting) and within the last 3 d of each dietary period (postprandial). alpha-Asp-Phe concentrations were below detection limits (0.5 mumol/L) in all plasma samples and Phe and Asp concentrations remained within normal limits, alpha-Asp-Phe hydrolase activities in baseline hemolysate samples did not differ between groups. One subject had a plasma alpha-Asp-Phe hydrolase activity > 2 SD below the mean. Despite this low activity, this subject did not show consistent cognitive or behavioral anomalies that could be linked to low hydrolase activity.