Some thyroid, rheumatic and hepatic diseases consistently have high female:male ratios, but many autoimmune diseases do not. Gonadal hormones, if they play a role in determining sex ratios, likely do so through a threshold or permissive mechanism. Sex differences related to X-inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences, exposures, vulnerable periods, or thresholds are alternative, theoretical, explanations for sex differences of incidence.