The 'hygiene hypothesis' has been proposed to explain apparent increases in autoimmune disease and allergy in areas of the world with improved health care and sanitation. This hypothesis proposes that the lack of serious childhood infections impairs development of an appropriately educated immune response. Imbalance of Th1 and Th2 responses and lack of regulatory T-cell populations are two of many proposed potential mechanisms for immune failures such as autoimmunity and allergy. We summarize the literature evidence for the influence of infectious organisms on autoimmunity with focus on helminth and mycobacterial infections. We also demonstrate that Schistosoma mansoni ova pretreatment, Mycobacterium bovis (BCG) infection, and lyophilized Mycobacterium tuberculosis all modify the course of clinical disease in mice induced for experimental autoimmune encephalomyelitis (a mouse model for human multiple sclerosis (MS)). Our data supports the applicability of the hygiene hypothesis to CNS autoimmune disease.