The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP<or=0.50 mg/dl, normal CRP group, N=21) on the PANSS total score, negative symptom subscale score and general psychopathology subscale score. There was no significant difference between the two groups on the PANSS positive symptom subscale score. An inflammatory process, as reflected by elevated serum levels of CRP, might be associated with more severe psychopathology in a subgroup of patients with schizophrenia.