Combined MAOI-tricyclic treatment remains a plausible approach to depressions refractory to single drugs. Adherence to published guidelines should minimize special risks of the combined treatment. However, such risks do exist, and should be borne in mind. Most severe reactions - characterized by hyperthermia, delirium, convulsions, and sometimes fatal outcome - have occurred after a tricyclic was added to established MAOI treatment. Combined treatment may be associated with a lower risk of hypertensive crisis than treatment with MAOI alone. There are no data from double-blind, control-group studies to demonstrate an advantage for the MAOI-tricyclic combination in refractory depression. However, almost no such data exist to establish the advantage of any other treatment in this clinical situation. Clinical experience provides the primary basis for continued consideration of this approach when usual treatments have failed.