The site-dependent, small intestinal absorption characteristics of ranitidine were estimated by the intestinal steady state perfusion technique (triple lumen tubing system) combined with simultaneous measurement of serum concentrations of ranitidine. Ranitidine 150 mg.l-1 was perfused at 10 ml.min-1 for 180 min in different sites of the small intestine between 65-250 cm beyond the teeth. Each of 9 healthy, male volunteers was examined twice, using perfusion sites in different regions of the small intestine to permit intraindividual comparisons. The absorption rates (micrograms.30 cm-1.min-1) calculated from intestinal samples showed distinct site-dependence; the highest rates (medians 160-923 micrograms.30 cm-1.min-1) were found in the most proximal region (duodenojejunal junction), and the most distal perfusion sites (distal jejunum/ileum) showed median rates from 193 to 265 micrograms.30 cm-1.min-1. In both of these regions there was a significant positive correlation between the net intestinal water flux and the movement of ranitidine. Within the mid-jejunum, every subject showed marked secretion of ranitidine into the gut lumen (medians -338 to -124 micrograms.30 cm-1.min-1), and in this region there was no influence of water flux on ranitidine movement. The intraluminal results were confirmed by the corresponding site-dependent areas under the serum concentration-time curves (AUC), which decreased with the distance of the perfusion site from the teeth. After the more distal perfusions individual AUCs amounted to 64-16% of the AUCs obtained after more proximal applications. The results demonstrate the small intestine as the site of a gradient of absorption of ranitidine.(ABSTRACT TRUNCATED AT 250 WORDS)