The authors have used transgenic mice to study the activity of a hybrid oncogene made up of 1.25 kb of 5' upstream sequences, derived from the bovine vasopressin gene, promoting the expression of the large T-antigen coding sequences of the early region of simian virus 40. Rather than promoting tumorigenesis in vasopressinergic cells of the hypothalamus, expression and activity of the hybrid oncogene, and consequent tumor formation, were confined to insulin-producing beta cells of the endocrine pancreas and to cells in the anterior pituitary. These observations suggest that the specificity of vasopressin gene expression normally results from an interaction between several regulatory elements, some of which are absent from the hybrid oncogene. The possible relationship between the endocrine tumor syndrome found in the vasopressin-SV40 transgenic mice and familial human multiple endocrine neoplasia is discussed.