Assessment of prefrontal brain cortex function can be helpful in treatment monitoring in patients with phenylketonuria. We aimed to assess the usefulness of computerized neuropsychological tests developed for handheld computers for this purpose. We observed worse test performance among persons with blood phenylalanine concentrations exceeding the recommended range. Use of handheld computers was assessed by patients and by doctors as interesting, not time-consuming and convenient. This method can be helpful during routine follow-up visits.