Von Hippel-Lindau disease is a rare, autosomal-dominant disorder characterized by CNS hemangioblastomas, retinal angiomas, renal cell carcinomas, pheochromocytomas, and visceral cysts. The occurrence of islet cell tumors in von Hippel-Lindau disease has been noted recently. Because of the coexistence of both islet cell tumors and pheochromocytomas in some patients with this disorder, it has been proposed that there may be a continuum of the multiple endocrine neoplasias. However, no large, multifamily study has been published evaluating the prevalence of islet cell tumors and pheochromocytomas in von Hippel-Lindau disease. To assess the frequency of islet cell tumors in this disorder and its relationship to the multiple endocrine neoplasias, we reviewed the clinical and imaging findings of all patients with von Hippel-Lindau disease evaluated at the Mayo Clinic between January 1979 and December 1989. Forty-three patients with von Hippel-Lindau disease from over 25 kindreds were found. Cross-sectional imaging of the pancreas had been performed in 35. Islet cell tumors were found in six (17%) of these, three islet cell adenomas and three islet cell carcinomas. No patient presented with endocrine-related symptoms; four tumors were detected during screening examinations of the abdomen. Two (33%) of these six patients had a coexisting pheochromocytoma. Our review of a large number of patients from many different families with von Hippel-Lindau disease revealed a high prevalence of islet cell tumors and the frequent coexistence of islet cell tumors and pheochromocytomas. This latter finding supports a continuum of the multiple endocrine neoplastic syndromes.