Two peripheral enzymes, dopamine-beta-hydroxylase (DBH) and monoamine oxidase (MAO), have previously been found to be altered in patients with tardive dyskinesia (TD). In order to examine whether these changes relate to the inherited component of enzyme activity or environmental factors, we assayed DBH and MAO activities in families of six TD probands and six matched non-TD probands. Five of six TD probands had DBH activity at least 50% greater than that of the family mean, whereas two of six non-TD probands had the same trend. No deviation from family means was suggested for MAO activity in the TD group. A study of chronic schizophrenic quadruplets with a history of prolonged neuroleptic treatment showed that only one quadruplet had TD. This quadruplet had plasma DBH activity four standard deviations above the means for her three siblings and three other family members. Our data do not support inheritance of predisposition to develop TD. The enzymatic alterations in TD patients do not seem to have been determined genetically, but they are probably a result of abnormal biochemical effects of prolonged neuroleptic treatment in those patients.