Recent studies have greatly increased the knowledge of the genetics of diabetes mellitus. At present several markers of the disease are under discussion. For insulin-dependent diabetes mellitus there is an association between markers of the histocompatibility complex and the incidence of the disease. The genes of the human histocompatibility complex code for at least three different classes of polymorphic proteins involved in the immune response. Two of them, the class I and the class II antigens are described in the article. The class II antigens are primarily expressed on special cells of the immune system. A typical feature of these antigens is their extensive polymorphism, which is the result of their genetic organization. The occurrence of insulin-dependent diabetes mellitus is more or less strongly associated with the class II antigen types DR3 and/or DR4. Using recombinant DNA technology it is possible to further characterize these and other class II specificities at genetic level. There are data on the occurrence of some class II antigen related DNA restriction fragments. They are much more strongly associated with the susceptibility to the disease than other markers found so far.