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The absorption of the model drug carbenoxolone was reevaluated using an in situ rat intestinal perfusion technique in which disappearance from the intestinal lumen, binding to the perfused jejunal segment, and appearance in the mesenteric (jejunal) vein were measured. The effect of the degree of ionization on these processes was examined by employing perfusion solutions of pH 4.0, 4.4, 5.0, and 6.5. Tissue binding was observed to be independent of pH. There was a rank-order correlation of the transfer rate of carbenoxolone with the degree of ionization which indicated that carbenoxolone was absorbed faster in its ionized form. This observation is in direct opposition to the pH-partition hypothesis, a finding which appears to support the previous work of Bridges et al. Ion-pairing of carbenoxolone with sodium ion present in the pH 6.5 buffer is one possible explanation for the unusually high transfer rate seen at this pH. A more likely explanation is that at the low pH values, some carbenoxolone precipitated out of solution during the perfusion experiments, thereby reducing the driving force for diffusion across the intestinal wall.