• Monitoring of 5-hydroxyindole (5-HI) levels in blood in hyperactive institutionalized mentally retarded patients before and after drug therapy revealed depression of 5-HI levels in 83% of hyperactive patients. In these patients with low serotonin levels, elevation of 5-HI levels in blood into the normal range by administration of a variety of psychoactive agents was associated with the disappearance of the hyperkinetic syndrome. Patients who remained hyperactive continued to have low 5-HI levels. Return of hyperactivity upon withdrawal of medication in patients who were previously well controlled was associated with a fall in 5-HI levels. Adverse responses were seen in these patients when they were treated with medications usually tending to lower 5-HI levels in blood. Medications used in the treatment of hyperactivity may be classified as to whether they usually elevate, lower, or have no significant effect on 5-HI levels in blood.