In this presentation I will present several critical issues in the image of serotonin transporter in bipolar disorders. However, most of time will spend on this article as an example. Objectives: Previous positron emission tomography studies have demonstrated that serotonin transporter (SERT) binding in the midbrain is decreased in the depressive state of bipolar disorder (BD). The aim of this study was to assess SERT binding in the midbrain of patients in a euthymic state of BD. Methods: Twenty-eight healthy controls and 24 patients in a euthymic state of medicated BD were recruited. Euthymic state was defined as a Montgomery-Asberg Depression Rating Scale scores less than 10 and a Young Mania Rating Scale scores less than 7 within a consecutive eight-week period. Single photon emission computed tomography with the radiotracer 123I-ADAM was used to measure SERT binding in the midbrain. An equilibrium ratio model was used for data analysis. Specific uptake ratio (SUR), which represents availability of SERT binding in the midbrain, was the primary measurement outcome. Results: The averaged SURs were not different between healthy controls and BD patients in euthymic state (p=0.27). However, a three-way ANCOVA analysis compared SURs in healthy controls, BD 1 and BD II covarying education duration and sex showed that the averaged SURs were significantly lower in BD I than BD II patients and healthy controls (p=0.042). The decreased SURs in BD I patients were well correlated with duration of illness (R=-0.742, p=0.014) only. Conclusions: Our findings demonstrate that there is differential biological regulation in BD I and BD II patients after stable treatment, which may support the existence of a dichotomy in BD.