The objective of this study tons to determine Me association between the patterns of change in the dopaminergic metabolite plasma homovanillic acid (HVA), the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and psychosis following haloperidol withdrawal in schizophrenic patients. Weekly plasma measurements were obtained in 107 subjects with schizophrenia or schizoaffective disorder. Random regression was used to control for individual variance while modeling metabolite changes over time and relationships with psychosis. Changes in plasma MHPG were not significantly associated with relapse or psychosis, while increased plasma HVA was found to be associated with relapse. Psychosis was correlated negatively with plasma HVA levels. The current analysis, controlling for individual variance, indicates that there is evidence for pharmacological effects an plasma HVA, but not plasma MHPG. In addition, these metabolites do not appear to be direct markers of psychosis, but may be associated with a compensatory response by the system to return to the steady state. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.