Hyporesponsive genetic variants of the melanocortin 1 receptor result in pigmentary phenotypes exhibiting light skin and light color hair, including red hair. These variants are common in populations with high rates of multiple sclerosis, while rare in populations with low rates. Alpha-melanocyte stimulating hormone, the major ligand for this receptor, is responsible for phenotype determination, but is also known for its anti-inflammatory and immune modulating effects, including inhibition of factors implicated in multiple sclerosis pathology. As the melanocortin 1 receptor is expressed on various cell types involved in immune response, it is possible that carriers of hyporesponsive variants of this receptor lack the full anti-inflammatory and immune modulating effects of alpha-melanocyte stimulating hormone. It is proposed that these variants are part of a spectrum of genes involved in the etiology of multiple sclerosis. Related aspects of multiple sclerosis epidemiology are examined.