Epilepsy is the most frequent additional handicap in mentally retarded persons. Brain injury and mental retardation may predispose to side effects of antiepileptic drugs (AEDs) on the central nervous system. 63 institutionalized mentally retarded patients were treated for epilepsy in the 1980s. AED treatment was carefully monitored, aiming at the lowest effective dose and an optimal balance between seizure control and adverse effects. In 15 patients, AEDs could be withdrawn. Drugs with less cognitive side effects, such as carbamazepine and valproate, were preferred to longer established drugs, such as phenobarbital and phenytoin. A pronounced decrease in the frequency of seizures was achieved during the study. Based on the calculated Defined Daily Doses, the prescription of AEDs was reduced by 18%. Phenobarbital constituted 39% of the AED consumption at the beginning and 7% at the end of the study. The corresponding figures for phenytoin were 20 and 16%. The fraction of carbamazepine increased from 31 to 44% and that of valproate from 6 to 32%. Less sedative side effects were reported. Several factors other than AEDs may have modified control of seizure in this long term study. These issues are discussed. After the reform of the system of care for the mentally retarded in Norway, it is a challenge to the health authorities to provide an adequate comprehensive epilepsy service to this group of patients.