Transport of lysine across the rat jejunum has been studied measuring transmural fluxes, Jms and Jsm, under short-circuit conditions, influx across the brush-border membrane, Jmc, under open-circuit and voltage-clamp conditions, and steady-state uptake by the isolated mucosa. 1. Jlysmc can be described as the sum of a saturable process with a Kt of 3 mM and a Jmax of 2.25 micromole/cm2.hr and a diffusional component corresponding to a lysine permeability of 0.014 cm/hr. Also Jlysms is well described as the sum of a saturable process and a diffusional contribution described by the same permeability as for Jlysmc. 2. The effects of the transmural p.d. on Jlysmc indicate that at 60 mM this flux includes a diffusional contribution, which corresponds to a lysine permeability of 0.014 cm/hr. 3. The passage of an electrical current across the gut wall changes the electrical conductance as expected for a cation-selective epithelium. The effect of a mucosa to serosa current on the Jms value of mannitol provides confirmation of the expected current effect on transepithelial volume flow. These effects on conductance and solute flux, together with the electrostatic effect on lysine movements, suffice to account for the p.d. effects on Jmc, Jms, and Jsm of lysine. 4. Jlyssm is in a saturable manner stimulated by increasing concentrations of D-glucose. At higher (10 mM) concentrations of lysine this effect leads to a net secretion of lysine. Qualitatively and quantitatively these effects are consistent with the model of a glucose-induced fluid circuit between the mucosal solution and the lateral intercellular spaces. 5. All observations are consistent with a paracellular, transepithelial pathway for lysine, which includes the lateral intercellular spaces. 6. The transport of lysine across the basolateral membrane is analysed. Togethet the data on transcellular passage of lysine are very similar to those reported for rabbit ileum, except that more than one transport process could not be demonstrated.