Coeliac disease (CD) is a malabsorption syndrome mediated by gluten toxicity. In almost all populations studied CD is strongly associated with HLA.DR3 and to a lesser extent with DR7, the frequency of DR2 is often low. There is a highly significant excess of DR3/DR7 heterozygotes. Although the association of CD with HLA has been known for 15 years the mode of transmission is poorly understood. In multiple case families the segregation of haplotypes is in favour of a recessive mode of inheritance with low penetrance. The rare cases of CD negative for DR3 and DR7 are positive for DR4 and negative for DQw2, ruling out the intervention of DQw2 by linkage disequilibrium. A recent study tends to show an hyporesponsiveness of T lymphocytes from patients to an antigenic extract of gluten.