Leukemia inhibitory factor (LIF) is a cytokine of the interleukin-6 family exhibiting diverse physiological functions during inflammatory stress. It is well known that syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is often associated with inflammatory disease, and cytokines produced at inflammatory foci are thought to stimulate arginine vasopressin (AVP) release. In the present study, we investigated the effects of centrally administered LIF on AVP release in conscious rats. Intracerebroventricular administration of LIF (0.01-1.0 microg/rat) significantly increased the plasma AVP concentration, and its effect was observed from 5 to 60 min after the injection. LIF did not cause significant changes in plasma Na+, total protein and blood pressure. There were no significant changes in the plasma AVP concentration after intravenous injection of LIF (1.0, 3.0 microg/rat). These results indicate that LIF plays a stimulatory role in the regulation of AVP release, and suggest the possibility that LIF may be involved in the pathogenesis of SIADH.