BDNF is a member of the neurotrophic family that promotes the development, regeneration, sustaining and maintenance of neuron function in the central nervous system. BDNF modulates neurotransmitter synthesis, metabolism and neuronal activity and is also involved in the development of dopaminergic-related systems, and the mesolimbic dopamine systems. In this study we aimed to investigate the possible differences of serum brain-derived neurotrophic factor (BDNF) levels between the drug-naive patients with schizophrenia and healthy controls. Serum BDNF levels were determined in the serum of 35 drug-naive patients diagnosed as schizophrenia according to SCID-I and DSM-IV-TR criteria and 35 healthy controls subjects matched for gender and age. The schizophrenia symptomatology was assessed by the positive and negative syndrome scale (PANSS). The results showed that BDNF levels were significantly lower in drug-naive patients with schizophrenia than in healthy control subjects (p=0.000). There was a significant difference in BDNF levels between disorganized and paranoid (p = 0.000), disorganized and undifferentiated schizophrenia (p = 0.000) subtypes. There was no significant difference in BDNF levels between the undifferentiated and paranoid schizophrenia subtypes (p = 0.081). The relationship between PANSS scores and subscale scores and serum BDNF levels was not found to be significant (p>0.05). The relationship between general assessment of functionality scores and serum BDNF levels was examined and there was a positive correlation between them (p = 0.07, r = 0.445). Our findings showed decreased BDNF serum levels in a sample of drug-naive patients with schizophrenia. Lower serum levels of BDNF in a sample of drug-naive patients with schizophrenia are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying in the initial phase of schizophrenia suggesting that neurodevelopmental disturbances may be involved in the pathogenesis of schizophrenia.