Background: Psychosis spectrum disorders, especially schizophrenia, have been linked to disturbed dopaminergic activity in the brain. Plasma homovanillic acid (pHVA) levels partly represent dopaminergic metabolism in the central nervous system. In the present study associations between (changes in) pHVA levels, symptom severity and symptomatic improvement in patients with psychoses were investigated. Methods: From a total of 80 patients, 58 fulfilled all inclusion criteria and their symptom profile and severity were assessed by means of the Comprehensive Assessment of Symptoms and History (CASH), the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale for Severity and Improvement (CGI-S/CGI-I) at baseline and after 6 weeks of antipsychotic treatment. After inclusion, all patients were prescribed first- or second-generation antipsychotics by their treating psychiatrist. A total of 12 patients had first-episode psychosis (FEP). At both time points, pHVA levels were measured. Subsequently, pHVA levels were compared with an age-matched control sample and changes in pHVA levels (ΔpHVA) after treatment were associated with clinical parameters. Results: Before analyses, data were scrutinized for possible confounders, particularly gender, smoking, medication status (including antipsychotic class), and recent drug use. The pHVA levels in patients were not different from those in controls. Treatment resulted in a significant decrease of all parameters. Symptomatic improvement as well as ΔpHVA was most pronounced in FEP patients. Conclusion: These findings show that patients with FEP have a more favourable outcome than non-FEP patients and that greater ΔpHVA also suggests that FEP patients still have the capacity to adjust dopaminergic neurotransmission.