Multiple low-dose injections of streptozotocin (STZ) induce a delayed but progressively increasing state of hyperglycemia in mice. Different inbred strains of mice show different susceptibility to this treatment. We examined whether genetic factors associated with the H-2 complex influence the susceptibility or resistance, using a selected group of 12 inbred and 5 congenie resistant strains of mice. We found that different congenie strains differed significantly in their susceptibility to STZ-induced diabetes, suggesting that H-2-asso-ciated genes do influence the susceptibility. However, at least some inbred strains sharing the same H-2 haplotype also differed in their susceptibility, indicating that genes outside the H-2 complex may also affect the susceptibility. Therefore, there appear to be at least two genes, one within and one or more outside the H-2 complex, that determine the susceptibility to multiple low doses of STZ.

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