From pluripotent pancreatic rat islet tumor tissue we have previously reported the isolation of stable transplantable glucagonoma tumor phenotypes in rats characterized by acute onset of anorexia. We now report that these tumors also cause severe adipsia. Food and water intake is reduced by more than 95% and is immediately cured upon tumor removal. Four anorectic tumor lines were all characterized as glucagonomas with high levels of proglucagon mRNA, and of two tested both were associated with highly elevated plasma levels of glucagon as well as of Glp-1(7-36amide) in the host rat. This fetal processing pattern of proglucagon may be indirectly linked to the anorectic phenotype, since we have now isolated a non-anorectic glucagonoma with similar levels of proglucagon mRNA. Lack of anorexia/adipsia in SV-40-T-antigen driven glucagonomas in transgenic mice with similar fetal processing as reported by other suggests that our tumors produce a novel anorectic substance. This factor ranges among the most potent of its kind as a peripheral mediator involved in appetite and thirst regulation. In summary, the glucagonomas provide an interesting tool with which to study the nature of severe anorexia as well as adipsia, and the identification of the active substance(s) may provide novel therapeutics for the treatment of obesity-related disorders such as NIDDM.