A dysfunction in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, possibly attributed to a change in glucocorticoid receptor (GR) functionality, has been implicated in depression. We have measured both lymphocyte GR receptor binding parameters and plasma sialyltransferase activity, as a biochemical marker of GR function, in two groups of patients suffering from depression or schizophrenia and in a group of age- and sex-matched controls. While there was a significant increase in plasma cortisol levels in the depressed group, there were no changes in the lymphocyte GR binding parameters (Km and Bmax). There was, however, a significant decrease in the plasma sialyltransferase: cortisol ratio in the depressed group suggesting an inability of the raised cortisol levels to induce enzyme expression and this ratio may provide a useful biochemical marker ofcortisol receptor function. Although there was an increase in the plasma activity of the α2,6 sialyltransferase isozyme in the schizophrenic group, no other changes were determined. Therefore, while the total plasma sialyltransferase: cortisol ratio reflects HPA axis function, alterations in specific isozyme activity may also be associated with other CNS disease states.