Multiple sclerosis is a central nervous system demyelinating disease. Significant evidence, including similarities with its animal model, experimental autoimmune encephalomyelitis, supports an autoimmune mechanism, activated by putative environmental factors in genetically predisposed individuals. Genetic factors strongly influence the susceptibility to demyelinating diseases in humans and rodents. Understanding the mechanisms governing susceptibility versus resistance may help to identify individuals at risk or design therapeutic strategies. The hypothesis formulated here is based on the observation that resistance to multiple sclerosis and experimental autoimmune encephalomyelitis is associated with dark skin pigmentation. While this may signify a protective role for melanin against environmental factors producing oxidative damage, the mechanism postulated here is that susceptibility to autoimmune demyelination is influenced by hormonal factors, i.e. the neurohormones melatonin and melanocyte stimulating hormone, which have opposing effects on immune functions and, the same time, are important determinants of the individual's production of melanin.