The mechanism ofβ-cell destruction leading to insulin dependent diabetes is probably a cell mediated autoimmune process occurring in genetically susceptible individuals. Since 50–70% of monozygotic twins will not get the disease non-genetic risk factors must play an important role in the etiology of the disease. During the past decade population based epidemiological studies have identified several risk determinants for insulin dependent diabetes. Based on these studies a multifactorial hypothesis of causation is proposed. Some risk determinants (maternal child blood group incompatibility, fetal viral infections, early exposure to cow's milk proteins, a high exposure level of nitrosamines) may independently initiate the autoimmune process by causing the initial damage of theβ-cell, leading to antigen release. Other risk determinants may promote an already ongoing autoimmune destructive process through induction of lymphokine release or by causing an increased work load on theβ-cell. Risk factors that may increase the peripheral need for insulin (infectious diseases, cold environment, a high growth rate and stressful life events) may act as promoters of theβ-cell destruction but also disclose theβ-cell impairment and make the disease clinically overt. Possibilities of different risk profiles in different age groups and of synergism between different risk factors are also discussed.