A number of lines of evidence support the hypothesis that ulcerative colitis is an inherited disorder in a proportion of cases. First, there is a pattern of familial aggregation. Second, there are differences in the prevalence of the disease in different ethnic groups. Finally, the concordance rate in monozygotic twin pairs is higher than that of dizygotic twin pairs, although not as high as the concordance rates observed in Crohn's disease. Genetic models of the inheritance patterns suggest that ulcerative colitis is probably caused by one major gene, although that gene (or genes) remains to be identified. While at least one localization for susceptibility to Crohn's disease now seems certain, efforts to localize and characterize the susceptibility genes involved in the inheritance of ulcerative colitis are still underway. While the genes of the major histocompatibility complex have been imputed as causal in susceptibility to ulcerative colitis, a consensus of proof continues to elude us.