Sodium flux from serosa to mucosa, JN, in rabbit ileum in vitro has been studied as a function of applied electrical potential at equal sodium concentrations in the bathing solutions. The results indicate that J involves two pathways, a diffusional flux through a paracellular shunt pathway and a flux that is independent of applied potential and presumably involves a transcellular pathway. The latter pathway comprises approximately 25 % of J in Ringer's solution containing 10 mM glucose and 25 mM bicarbonate. It is stimulated significantly by theophylline unaffected by removal of glucose or addition of ouabain but is reduced to negligible values by anoxia, dinitrophenol, and replacement of all chloride and bicarbonate by isethionate. Thus this component of J:L has a number of characteristics consistent with involvement in a specific secretory process mediating an electrically neutral secretory transport of sodium plus anion from serosa to mucosa. In addition to stimulating this process, theophylline significantly reduced the permeability of the paracellular shunt pathway to sodium.Recent studies on ion transport across rabbit ileum have raised certain questions about mechanisms involved in movement of ions from the serosal to the mucosal side of the tissue. For example, Frizzell and Schultz (1) have suggested that nearly all of the Na flux from serosa to mucosa across in vitro preparations of rabbit ileum occurs via the intercellular shunt pathway they have described (see also Rose and Schultz [2]). On the other hand, Powell et al. have proposed that there may be an active secretory process for Na in guinea pig ileum (3) and rabbit ileum (4, 5) that accounts for a part of the observed serosal-to-mucosal flux and that this process may be stimulated by cholera toxin (6) and theophylline (5). Such a process might be expected to involve transcellular movement of Na and would not be consistent with purely passive Na movement from serosa to mucosa via a shunt pathway. The situation is further complicated by the suggestion of Field et al. (7,8) that the THE JOURNAL OF GENERAL PHYSIOLOGY