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Background: Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite that causes persistent infection in humans. A substantial literature suggests that schizophrenia is associated with increased seroprevalence of T. gondii, but a possible link of the parasite with mood disorders has not been as thoroughly investigated. Methods: We examined the association of Toxoplasma-specific immunoglobulin G results with mood disorder outcomes in 7440 respondents from the third National Health and Nutrition Survey, which is a nationally representative sample of the United States noninstitutionalized civilian population. Regression models were adjusted for numerous potential confounders, including tobacco smoking and C-reactive protein levels. Results: No statistically significant associations were found between T. gondii seroprevalence and a history of major depression (n = 574; adjusted odds ratio [OR]:.8; 95% confidence interval [CI]:.5-1.2), severe major depression (n = 515; adjusted OR:.8; 95% CI:.6-1.2), dysthymia (n = 548; adjusted OR: 1.1; 95% CI:.7-1.8), or dysthymia with comorbid major depression (n = 242, adjusted OR: 1.2; 95% CI:.6-2.4), all p values were > .05, including analysis stratified by gender. However, there was a significant relationship between T. gondii seroprevalence and bipolar disorder type I for respondents in which both manic and major depression symptoms were reported (n = 41; adjusted OR: 2.4; 95% CI: 1.2-4.8; p < .05). Conclusions: In a population-based sample, T. gondii seroprevalence is not elevated in unipolar mood disorders but is higher in a subset of respondents with a history of bipolar disorder type 1.