The hygiene hypothesis proposes that several chronic inflammatory disorders (allergies, autoimmunity, inflammatory bowel disease) are increasing in prevalence in developed countries because a changing microbial environment has perturbed immunoregulatory circuits which normally terminate inflammatory responses. Some stress-related psychiatric disorders, particularly depression and anxiety, are associated with markers of ongoing inflammation, even without any accompanying inflammatory disorder. Moreover, pro-inflammatory cytokines can induce depression, which is commonly seen in patients treated with interleukin-2 or interferon-alpha. Therefore, some psychiatric disorders in developed countries might be attributable to failure of immunoregulatory circuits to terminate ongoing inflammatory responses. This is discussed in relation to the effects of the immune system on a specific group of brain serotonergic neurons involved in the pathophysiology of mood disorders.