Of 22 immunomodulatory substances screened 12 were effective in modulating the course of hyperglycemia following low dose streptozotocin treatment. In this animal model diabetes is induced by administration of low doses of streptozotocin (30-40 mg/kg) body weight to male C57BL/6J/Bom, C57BL/KsJ and C3H/He/Bom mice on 5 consecutive days. Conventional immunosuppressants (azathioprine, cyclophosphamide) largely protected from diabetes development. Partial suppression of hyperglycemia was also seen after administration of B. pertussis, fetal tissue extracts, FTS, inosine pranobex, metronidazole and ADA 202-718. The majority of these substances, when applied with another regimen, and TP5 caused enhancement of diabetes. In conclusion, several substances with a therapeutic potential in experimental diabetes have been identified. Those with little risk of side-effects may deserve further analysis.