Differences in extent of amoxicillin absorption from various regions of the gastrointestinal tract were determined and compared with the same dose administered orally. Nine healthy men were intubated at a proximal (duodenum or jejunum) or distal (ileum or colon) site with use of a 15-foot double lumen nasointestinal tube. Amoxicillin solutions (375 mg in 120 ml water) were delivered on 2 successive days as a bolus or a 4-hour infusion. Subjects were reintubated at another site and amoxicillin administration was repeated. Subjects with colonic intubation received only infusions. Finally, all subjects received an oral dose of amoxicillin solution. Plasma samples were obtained at 16 time points over a 10-hour period and assayed for amoxicillin by use of an HPLC method. Area under the concentration-time curve and the maximum plasma concentration were computed to evaluate amoxicillin absorption. Amoxicillin absorption was rate and site dependent in the gastrointestinal tract. The drug was well absorbed in the duodenum and jejunum, with no significant differences in absorption when administered as a bolus or 4-hour infusion, but absorption was decreased and rate dependent in the ileum, where more drug was absorbed as an infusion compared with a bolus. Amoxicillin was unabsorbed when infused in all colonic regions.