Human lymphocytes obtained from fasted adult subjects and cultured human tumor lymphocytes were investigated for specific insulin receptors. By use of monoiodoinsulin, specific insulin binding sites were demonstrated in peripheral human lymphocytes, cultured human lymphocytes, and in other types of human circulating cells. Insulins and insulin derivatives that varied in their potency to stimulate glucose oxidation in the fat cell and to inhibit binding of [(125)I]insulin to purified plasma membranes, varied in an analogous fashion in their ability to inhibit the binding of labeled insulin to human lymphocytes. Hormones that had no effect on the binding of insulin to fat cells or liver membranes also had no effect on the binding of insulin to lymphocytes. Binding was time and temperature dependent; dissociation of [(125)I]insulin was rapid upon addition of 10 muM insulin. These findings afford a direct approach to the study of endocrine disorders in man.