Lumbar CSF HVA, MHPG, 5HIAA, cAMP and cGMP were measured in 12 chronic schizophrenics with tardive dyskinesia (TD) before and 3 weeks after sodium valproate (VPA) or cyproheptadine treatment. The amount of medication was kept constant throughout the study. Three of the 7 patients treated with VPA and 1 of the 5 with cyproheptadine showed improvement. HVA levels significantly decreased and cAMP and cGMP levels significantly increased. MHPG levels increased significantly during the treatment with VPA but declined during cyproheptadine treatment. There were no significant correlations between the degree of improvement in TD and the changes of amine metabolites or cyclic nucleotides. None of the pre-treatment values for CSF amine metabolites or cyclic nucleotides were different from those of 15 chronic schizophrenics without TD as controls. Decrease in HVA and increase in cGMP during the treatment might indicate the normalization of dopaminergic-cholinergic imbalance in the brain. Furthermore, amine metabolites and cyclic nucleotides were measured in 5 chronic schizophrenics with parkinsonian tremor. Low HVA and 5HIAA levels and high cAMP levels were observed in tremor group. However, only 5HIAA levels in tremor group were significantly lower than those in age-matched control group. It is suggested that neuroleptic-induced tremor may be attributed to serotonergic dysfunction in the brain.