Clara cell protein (CC16) and transferrin receptor (TfR) have been reported as possible biological markers for major depression and schizophrenia. However, the alternations of plasma TfR and CC16 levels and the influences of numerous clinical variables on them during bipolar mania are not sufficiently described. We investigated the immune function of 36 bipolar I, manic (DSM-IV) patients with Young Mania Rating Scale (YMRS) scores > or =26 as well as during the subsequent remission (YMRS < or =12) and age- and sex- matched healthy controls. The plasma TfR levels were increased during acute mania along with subsequent remission and were independent of medication status, individual variations, clinical and erythrocyte variables. Among inflammatory parameters and haematological variables, the plasma TfR levels merely had significant and negative relationship with the percentage of monocyte in circulating leukocyte counts despite of elevated plasma soluble interleukin-2 receptors levels during bipolar mania. The plasma levels of CC16 of bipolar patients did not significantly alter during acute mania, whereas smoking, body mass index, and co-existing psychotic features collectively contributed 42% of the plasma levels of CC16. We provide additional evidence to indicate the pathophysiological role of the immune systems in affective disorders. It is suggested that the elevation of plasma TfR levels might be a trait phenomenon in bipolar disorder.