This study evaluates the relationship between plasma homovanillic acid (pHVA) levels, which have been used to study the role of central dopamine in schizophrenia, and the positive/negative syndrome in first episode schizophrenic patients before and after antipsychotic treatment. Forty neuroleptic-naive first episode schizophrenic patients were monitored at baseline and on days 7, 14 and 28. Clinical status was evaluated with the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Brief Psychotic Rating Scale. Plasma HVA levels were also measured. Patients were divided into predominantly positive or negative syndrome groups by subtracting SAPS from SANS scores, at baseline. A healthy control group was also enrolled. Schizophrenic patients as a group had significantly higher pHVA levels than controls at baseline (20.50+/-11.85 vs. 13.04+/-7.22 ng/ml). Moreover, 12 predominantly negative syndrome patients had similar mean baseline pHVA levels (21.30+/-12.36 ng/ml) to those of 28 predominantly positive syndrome patients (19.40+/-11.33 ng/ml). During follow-up, there was a different evolution of pHVA levels in the predominantly positive syndrome group than in the predominantly negative syndrome group, with a significantly greater global reduction of pHVA levels in the former. Although both groups showed clinical improvement following 4 weeks of treatment with risperidone, pHVA levels at endpoint were lower (13.29+/-5.91 ng/ml) than at baseline in patients in the predominantly positive syndrome group, while among those in the predominantly negative syndrome group there was no difference in pHVA levels before and after treatment (21.02+/-13.06 ng/ml). The different pHVA level profiles observed in predominantly positive and negative syndrome first episode patients after 4 weeks of treatment with risperidone suggest that each syndrome may have a different underlying neurobiology.