Abstract There is substantial evidence suggesting that individual variability in antipsychotic treatment response could be genetically determined. Variations in several serotonin transporter ( 5-HTT) gene polymorphisms have been associated with antipsychotic response among chronic patients with schizophrenia, although their implication in early response among first-episode patients remains unclear. Two polymorphisms in the 5-HTT gene (a 44 bp insertion/deletion in the promoter region and the functional polymorphism rs25531) were genotyped in a sample of 147 drug-naïve patients experiencing a first episode of a non-affective psychosis. Early (6 weeks) response to antipsychotic treatment with haloperidol, olanzapine or risperidone was assessed with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. No clear association was found between the rs25531 variant and treatment response. However, significant associations were observed between 5-HTT-LPR variants and early negative symptom response among first-episode patients with psychosis. Our results suggest a minor contribution to antipsychotic drug response of genetic alterations in the 5-HTT gene.