To explore the contribution of infectious exposure to schizophrenia, we determined the levels of several antibodies to infectious agents in blood samples collected in a randomized double-blind 52 week clinical trial in China. The sample included 160 first-episode schizophrenia patients and 60 normal controls balanced in distribution of age (28 ±7), gender (53% male vs. 47% female) and birth place (48% urban vs 52% rural). The levels of 9 antibodies, including IgG class antibodies to Herpes Simplex Virus Type 1 and 2, Human Herpesvirus Type 6, Cytomegalovirus, Borrelia, Hantavirus, as well as IgG, IgM and IgA class antibodies to the protozoan Toxoplasma gondii (Toxo) were assayed with enzyme immunoassay. Toxo IgG was found to be significantly elevated in schizophrenia patients compared to unaffected controls (p=0.01). Furthermore, we found that patients with high Toxo IgG had more severe negative symptoms at baseline shown by SNAS total score (p=0.01) and its subscales on poverty of thought (p=0.04), apathy (p=0.03), and attention deficit (p=0.02). For cognitive functioning measured by WAIS-R, Toxo IgA correlated with poorer overall IQ (p=0.01) as with both performance IQ (p=0.01) and verbal (p=0.03). This may suggest some first-episode patients underwent infection with Toxoplasma in the recent past. We also explored the relationship between antibody levels and treatment response. Interestingly, high Toxo IgG levels significantly reduced the improvement in BPRS total score (p=0.002), SNAS total score (p=0.002) in patients treated with clozapine while the effectiveness of chlorpromazine was largely unaffected by the Toxo IgG level. These findings area consistent with the known effects of Toxoplasma gondii on brain development and provide the rationale for the evaluation of specific medication regimens for individuals who have undergone recent infection with this organism.