Patients with renal insufficiency suffer from inhibited glucose utilization which can be tested in vitro by the incubation of tissues or isolated cells in diluted uraemic serum. 1. Systematic isolation from the serum of patients with renal insufficiency has revealed that hippurate participates in the inhibition of glucose utilization in the muscle and, to a lesser extent, in the kidney. It does not inhibit glucose utilization in the brain, red blood cells and platelets. 2. Maximal inhibition is 86.6% and AD50 is 0.432 mmol hippurate/l. These hippurate concentrations are achieved in the early stages of renal insufficiency. 3. While the inhibitory effect is evident at normal and elevated glucose concentrations, it does not manifest itself at hypoglycaemic concentrations. 4. A less pronounced inhibitory effect, compared with hippurate, is exerted also by O-OH hippurate, but it is absent altogether in P-amino-hippurate and O-OH hippuryl-beta-glucuronide. It is concluded that, through its inhibition of glucose utilization, hippurate may participate in the development of muscular weakness in patients with renal insufficiency.