Stress, distress and a variety of psychiatric illnesses, notably the affective disorders, are increasingly reported to be associated with immunosuppression. The concept that psychic distress may predispose to medical illness is centuries old but has only recently attracted the attention of the scientific community at large. Interdisciplinary collaboration has established psychoneuroimmunology, or neuroimmunomodulation, as a new field of investigation with the goal of rigorous scientific research into the elusive mind-body connection. This has resulted in the rapid accumulation of information which falls across the boundary lines of psychiatry, immunology, neurosciences and endocrinology. Here David Khansari, Anthony Murgo and Robert Faith review the effects of stress on the endocrine and central nervous systems and the interactions between these systems and the immune response after exposure to stress signals.