1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy.
2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH.
3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused.
4. In one subject intravenous infusion of [15N]-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal.
5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesting limited permeability of the colonic mucosa to urea.
6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of ‘juxtamucosal’ (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed.