Evidence implies that hormonal factors are involved in susceptibility to multiple sclerosis. Diseases associated with a class II allele occur more frequently in women than in men. Multiple sclerosis is more frequent in women, particularly in the early- and late-onset groups. Pregnancy has a favorable effect on the course of multiple sclerosis on both a short- and a long-term basis. Experimental allergic encephalomyelitis, an animal model with similarities to multiple sclerosis, is also influenced by hormonal factors in both occurrence and severity. The multiple levels of interaction between immune, endocrine, neurologic, and genetic systems probably explain the action of sex steroids in multiple sclerosis susceptibility.