There has been an increasing interest in the role of the immune and inflammatory systems in mood disorders. Mood episodes are associated with changes in acute phase proteins such as high-sensitivity C-reactive protein (hsCRP). The present study investigated serum hsCRP in manic, depressed, and euthymic BD patients as compared to matched healthy controls. Serum hsCRP was assessed using an ultrasensitive assay of particle-enhanced immunoturbidimetric latex agglutination. Serum hsCRP levels were increased in manic BD patients, as compared to euthymic, depressed patients and healthy controls (P < 0.001). These findings add to the notion that changes in the inflammatory system take place during acute episodes of mania.