BICARBONATE MAY BE SECRETED INTO THE INTESTINAL LUMEN IN CHOLERA BECAUSE: HCO(3) (-) ions are transported, or because OH(-) ions accumulate and react with dissolved CO(2) to form HCO(3) (-). If HCO(3) (-) ions are transported into the lumen from the interstitial fluid, lumenal P(CO2) should increase (HCO(3) (-) right harpoon over left harpoon OH(-) + CO(2)); if OH(-) accumulates, P(CO2) should diminish. Net movement of H(2)O, and HCO(3) (-), and changes in pH and P(CO2) in lumenal fluid were studied in adjacent segments of rabbit ileum in vivo, one of which was exposed to choleragen. 4 h after exposure, segments were drained and infused with gassed Krebs-Henseleit solution whose P(CO2) exceeded arterial P(CO2). After 45 min, fluid was collected anaerobically from control and cholera segments. Among 13 cholera segments, lumenal P(CO2) diminished by a mean of 8.4 torr and was less than femoral arterial blood in six instances. In the paired control segments, mean P(CO2) increased by 4.4 torr, and was always greater than arterial P(CO2). Dilution could not account for the low P(CO2) in cholera segments because in hypertonic solutions that caused water to move into the lumen, the P(CO2) did not differ from control values obtained with isotonic solutions. The results suggest that OH(-) accumulation (by addition of OH(-) or removal of H(+)) causes HCO(3) (-) secretion in cholera. This does not result from secretion of some other base (e.g., HPO(4) (-)), because HCO(3) (-) accounts for most of the base in the lumenal fluid. The P(CO2) changes suggest that OH(-) reacts with CO(2) at the cell-lumen interface, but reaction at the cell-interstitial fluid interface cannot be excluded.