The effect of phenformin on the uptake of glucose and water by isolated full-thickness sheets of human ileum has been studied. A significant decrease in mucosal glucose uptake was found, and significant glucose translocation to the serosal surface was abolished. This was accompanied by a proportional decrease in the production of lactate and in the net transport of water across the tissue. The magnitude of the observed changes does not support the hypothesis that overt glucose malabsorption is of significance in the therapeutic action of phenformin but confirms previous observations that the kinetics of absorption of a glucose load may be altered.