Cerebrospinal fluid HVA, MHPG, 5HIAA, cAMP and cGMP were measured in 12 chronic schizophrenic patients with tardive dyskinesia before and after the administration of oxypertine, hydroxyzine pamoate or placebo. Lumbar puncture was performed after probenecid administration. HVA levels significantly decreased and cAMP levels significantly increased after oxypertine treatment. Three of the four patients treated with oxypertine showed improvement in tardive dyskinesia. 5HIAA levels significantly decreased during hydroxyzine administration. Two of the four patients improved in tardive dyskinesia showed decrease of HVA after hydroxyzine treatment. There were no significant alterations of amine metabolites and cyclic nucleotides in the patients with placebo. Decrease of HVA may indicate the normalization of hyperdopaminergic state. It has been recognized that oxypertine is a noradrenaline depleting agent and hydroxyzine has an antiserotonic and antihistaminic properties. Noradrenaline and/or serotonin may have an effect on dopaminergic function in the central nervous system.