Increasing evidence suggests that altered immune functions are related to the pathophysiology of schizophrenia. Relatively little information is available on Toll-like receptors (TLRs), which are implicated in the recognition of molecular patterns associated with pathogens and internal cellular damage signals. By using immunophenotyping and flow cytometry, we investigated TLRs in CD14+ monocytes, CD4+CD25 +Foxp3+ regulatory T cells (T-reg), and CD3+CD4+CD25+ activated T cells (T-act) in 35 drug-naive patients with schizophrenia before and after an 8-week period of antipsychotic treatment with risperidone or olanzapine. As compared with 30 healthy control individuals, drug-naive patients with schizophrenia exhibited an increased percentage of TLR4+ and TLR5+ monocytes and TLR5+ T-reg/T-act cells. At the end of the treatment period, we observed normalized TLR4+ monocytes and an up-regulation of TLR2+ monocytes and T-reg/T-act cells. Mean fluorescent intensity values, indicating receptor density, were consistent with these findings. In the drug-naive state, but not after treatment, higher percentages of TLR4+ and TLR5+ monocytes were correlated with more severe cognitive deficits. Positive, negative, and general clinical symptoms were not associated with TLRs. There were no significant differences between patients receiving olanzapine and risperidone. These results indicate that abnormal expression of TLR5 can be detected in the earliest stage of schizophrenia, which is modulated by antipsychotics. Immunological alterations in unmedicated schizophrenia patients may be linked to cognitive deficits. (C) 2016 Elsevier Inc. All rights reserved.