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However, there have been fewer studies of patients with acute bipolar depression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Blood samples were obtained from individuals with acute bipolar depression, acute mania, and controls. These samples were evaluated for antibodies to human herpesviruses, gliadin, <jats:italic>Toxoplasma gondii<\/jats:italic>, and endogenous retroviruses as well as for C\u2010reactive protein (<jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content>) and pentraxin\u20103 using immunoassay methods. Linear regression models were used to compare the levels of the markers controlling for demographic and clinical variables. A subset of the bipolar depressed group was evaluated at a 6\u2010month follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The sample consisted of 82 individuals with acute bipolar depression, 147 with acute mania, and 280 controls. The levels of <jats:styled-content style=\"fixed-case\">CRP<\/jats:styled-content> and IgG antibodies to an endogenous retrovirus, Mason\u2010Pfizer monkey virus (<jats:styled-content style=\"fixed-case\">MPMV<\/jats:styled-content>), were significantly elevated in the bipolar depressed group. Levels of pentraxin\u20103 were reduced in both psychiatric groups. An evaluation of 32 individuals 6\u00a0months after hospitalization for bipolar depression showed a significant decrease in the levels of <jats:styled-content style=\"fixed-case\">MPMV<\/jats:styled-content> antibodies, but not a change in the other markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Individuals with acute bipolar depression show immune alterations. 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