The aim of the present study was to examine the effect of glibenclamide on the insulin receptors, the insulin sensitivity and the insulin secretion in obese non-ketotic diabetics. Two groups of 9 obese diabetics were studied before and after 10 days' treatment with a 1200 kcal's diet and a 1200 kcal's diet + 10 mg/day of glibenclamide, respectively. In the group treated with diet alone we found no significant alteration of the insulin secretion pattern (P greater than 0.1). However, the insulin sensitivity increased 37% (P less than 0.01). Furthermore, the insulin binding to monocytes increased (P less than 0.01) due to a 36% rise of the binding affinity. In the group treated with glibenclamide and diet the insulin secretory pattern was unchanged, too (p greater than 0.1). The insulin sensitivity, however, increased 83% (P less than 0.01). Moreover, the insulin binding was raised (P less than 0.01) as a result of a 80% rise of the number of insulin receptors. In 4 patients who were treated with diet (1200 kcal/day) plus glibenclamide and in 5 patients who were treated with diet alone (1200 kcal/day) the insulin binding to monocytes was studied during treatment for 1 year. After 1 year we found a significantly (P less than 0.005) higher cellular insulin binding in the glibenclamide treated patients compared to the patients who got diet alone. We conclude that 1) the augmentation of the insulin sensitivity is of great importance for the normalization of the diabetic state in obese, 2) the increase in insulin binding may be of importance for the increase in insulin sensitivity, 3) glibenclamide appears to enhance the insulin sensitivity through an increase in the number of insulin receptors.