Tissue insulin sensitivity was measured by the glucose clamp technique in 8 uremic insulin-dependent diabetic patients before and after 3 months on a low-protein diet (LPD) providing daily 35 kcal/kg body weight, 60% of the caloric supply being obtained from carbohydrates. An improvement in tissue insulin sensitivity was observed for each steady state of the clamp and daily insulin requirements decreased significantly from 38.3 +/- 3.2 to 28.2 +/- 2.5 units (p less than 0.01) in spite of an increased carbohydrate intake. It is suggested that LPD lowers the production and accumulation of uremic toxins interfering with insulin sensitivity.