A significant internal disorder is present in only a limited number of patients with essential pruritus. The mechanisms for the production of pruritus in these disorders are poorly understood and frequently are unrelated to liberation of histamine. Proteolytic enzymes in lymphoproliferative disorders, bile acids in obstructive hepatobiliary disease, parathyroid hormone in chronic renal failure, and prostaglandins and kinins are but a few of the chemicals that may ultimately be responsible for the development of pruritus in these and other purely cutaneous disorders. Patients with essential pruritus should have a comprehensive physical and laboratory evaluation, but psychologic, environmental, and other factors must be considered when thorough clinical evaluation is unrewarding. Treatment should be directed towards elimination of the underlying alteration, control of the additional factors, and alleviation of the symptom.