Recently, the synthetic immunomodulator Linomide (quinoline-3-carboxamide, LS 2616) was reported to prevent IDDM and insulitis in NOD mice. The mechanism for this protective effect is not known. The cytokine interleukin 1 (IL-1) may be a pathogenetic factor in the initial destruction of theβ-cells leading to IDDM. This study was undertaken to investigate the influence of Linomide on IL-1βinduced diabetogenic and hormonal changes in the ratin vivo, and on IL-1βmediated synthesis of NO and inhibition of insulin secretion in isolated islets of Langerhansex vivo.Normal male Wistar Kyoto rats received 4.0μg/kg of recombinant human IL-1β(rhIL-1β) i.p. daily for 5 days with or without Linomide (8-9 mg/kg/day) in the drinking water. Litters of neonatal Wistar rats were pretreated for 3 days with injections of 10 mg/kg of Linomide i.p., and pancreatic islets of Langerhans were isolated forex vivostudies. Linomide alone caused significant hypercorticosteronemia, hypoglucagonemia, lymphopenia and neutrophilia. Linomide had no effect on IL-1βinduced hyperglycemia, hyperglucagonemia, lymphopenia, neutrocytosis, or hypercorticosteronemia on day three and hypocorticosteronemia on day five. Further, Linomide did not prevent rhIL-1βmediated reduction in insulin secretion or increase in NO synthesisex vivo.In conclusion, Linomide does not seem to exert its protective effect on IDDM development via inhibition of interleukin 1 action on islet insulin release or NO production, but the increase in plasma corticosterone may contribute to the understanding of the immunomodulatory effects of Linomide.