New evidence that metformin increases intestinal glucose metabolism has necessitated a re-examination of the effect of metformin on intestinal glucose absorption. Normal 18 h fasted mice received an intragastric bolus of metformin 2 h before preparation of everted gut sacs from the proximal, middle and distal regions of the jejunum and ileum. Net mucosal glucose transfer from the intestinal lumen into the tissue was reduced by 15 and 28% after 50 and 250 mg kg-1 metformin, respectively (ANOVA, P less than 0.05). Net glucose transfer into the serosal fluid was reduced by 12 and 70% after 50 and 250 mg kg-1 metformin respectively (ANOVA, P less than 0.05 and P less than 0.01). The inhibitory effect of metformin on both the mucosal and serosal glucose transfer mechanisms was greatest in the middle portion of the small intestine. The results suggest that metformin decreases intestinal glucose absorption in a dose-dependent manner by effects on mucosal and serosal glucose transfer.