The CSF levels of HVA and 5-HIAA were determined in 90 drug-free DSM-III-R schizophrenic patients and 47 healthy control subjects, and their predictive value for 5-year outcome was evaluated. CSF was collected by lumbar puncture at index admission, and in 37 of the patients a second sample was drawn after approx. 7 weeks of neuroleptic treatment. Outcome was rated prospectively 5 years after index admission by means of the Strauss-Carpenter outcome scale. Schizophrenic patients had significantly lower levels of HVA in the CSF than the control group, but no difference was found for 5-HIAA. The CSF-amine metabolite levels were not correlated with age at admission, age at first symptoms or duration of the disorder. Neither HVA nor 5-HIAA correlated with the total outcome scores at a 1- and 5-year follow-up evaluation. First-admitted previously untreated patients with the poorest 5-year outcome had significantly lower HVA/5-HIAA quotients than those with a good outcome. Furthermore, patients still having a low HVA/5-HIAA quotient after treatment with neuroleptics had a poorer 5-year outcome than patients with an increased quotient. The data indicate that both HVA and 5-HIAA in the CSF, and especially their sensitivity to neuroleptic treatment, have a predictive value for the prognosis in schizophrenia.