It has been postulated that altered interleukin (IL) regulation may be involved in the pathogenesis of schizophrenia. We therefore investigated the relationships between interleukins, neurotransmitters, and psychopathology in schizophrenia. IL-1beta, IL-2, IL-6, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the plasma of neuroleptic-free male schizophrenics in comparison to age-matched healthy male controls (n=25 each). The patients' psychopathology was assessed by the Scale for the Assessment of Positive and Negative Symptoms (SAPS, SANS). The above variables were measured during acute states of illness and after eight weeks of treatment with haloperidol. The plasma levels of IL-2 and HVA were significantly higher in patients compared to controls. In schizophrenic patients, there were significant correlations between IL-2 and HVA, IL-2 and SAPS, and HVA and SAPS during the acute state of illness. The level of IL-6 was significantly correlated to SANS and duration of illness. In schizophrenic patients, the plasma levels of IL-2 and HVA were significantly lowered after treatment with haloperidol. Changes in IL-2 and HVA significantly correlated to those in HVA and SAPS, respectively. These results strongly suggest that the cytokines may modulate dopaminergic metabolism and schizophrenic symptomatology in schizophrenia.