Cortisol-binding globulin (CBG) is an alpha-1-glycoprotein with high affinity for cortiso that could be a potential biological marker of chronic stress, according to several previous studies. In order to examine CBG concentrations in bipolar disorder, we determined serum CBG levels by radioimmunoassay with monoclonal antibodies in a sample of 39 RDC bipolar I patients in remission and 21 healthy age-, sex- and weight-matched control subjects. Only lithium treatment was permitted. Plasma cortisol and serum lithium levels were also determined. Bipolar males showed statistically significant lower serum CBG levels than controls, whereas women showed very similar values. No correlation was found between CBG levels and cortisol or lithium concentrations. It is concluded that CBG levels are affected by chronic affective illness, even during remission periods, at least in bipolar males.