Schizophrenia is characterized by pathophysiological alterations of multiple neurotransmitter systems such as dopaminergic, glutamatergic, GABA-ergic and serotonergic pathways. Adenosine, a homeostatic neuromodulator that mediates signaling through multiple neurotransmitter pathways, is an emerging candidate neurobiological substrate of schizophrenia. The present study examined peripheral blood levels of adenosine deaminase, an adenosine metabolizing enzyme, in 16 neuroleptic-naive patients with recent-onset schizophrenia (mean age = 25.59 years (range: 16-35)) and 18 age-matched healthy comparison subjects (mean age = 25.17 years (range: 18-28)). Serum adenosine deaminase levels were assayed at two time points; before (7 p.m.) and after (7 a.m.) sleep. The adenosine deaminase levels were compared between groups and were correlated to positive and negative symptom severity measures. Adenosine deaminase levels were found to be higher at both evening (p=0.013) and morning (p<0.001) time points in our sample of patients with recent-onset schizophrenia who were never exposed to neuroleptic medications. Correlational analysis revealed evidence for a possible link between evening rise in adenosine deaminase and severity of auditory hallucinations (p=0.003) as well as morning rise in adenosine deaminase and severity of avolition-apathy in patients with schizophrenia (p=0.013). The results of the study provide strong support to the adenosine hypothesis of schizophrenia and highlight the potential utility of serum adenosine deaminase as a peripheral biomarker of schizophrenia.