Oral glucose tolerance in 11 normal subjects was significantly improved after peroral administration of 150 mg of butyl-biguanide. 2. On the other hand maxiumum capacity of renal glucose reabsorption (TmG) and lowest glomerular glucose filtration rate at which glucosuria was recorded (F min) remained uninfluenced after 150 mg of butyl-biguanide in 7 normal subjects. 3. These results are compatible with the hypothesis that the oral administration of therapeutic doses of biguanides yields concentrations at the luminal face of the intestine which inhibit glucose resorption. Plasma concentrations following oral intake of the same dose of biguanide are too low to exert any inhibiting action on renal glucose reabsorption as demonstrated by the present in vivo studies. 4. Urinary flow rate and inulin clearance remained unaltered after butyl-biguanide in these normal subjects.