In humans, deficiency of chloride and potassium were found to perpetuate the hyperbicarbonatemia that attends metabolic alkalosis induced by gastric aspiration partly by increasing renal bicarbonate reabsorption, commensurate with the attendant increase in filtered bicarbonate load, and partly by decreasing glomerular filtration rate (GFR), which minimizes the degree of which the filtered bicarbonate load increases and thereby minimizes the requisite increase in bicarbonate reabsorption. The relative contribution of stimulated renal bicarbonate reabsorption might increase, however, if the supply of extrarenal bicarbonate is increased, in which case a greater degree of hyperbicarbonatemia would be sustained. To investigate that possibility, we reexamined the mechanism of perpetuation of gastric alkalosis in normal subjects eating a low NaCl diet supplemented with bicarbonate salts. Prior to gastric aspiration, plasma bicarbonate concentration ([HCO3]p) and pH were higher than in similarly studied subjects not receiving bicarbonate: 29.9 ± 0.6 vs. 25.3 ± 0.1 and 7.43 ± 0.008 vs. 7.41 ± 0.002 mEq/1, respectively. With continued bicarbonate supplementation, gastric aspiration induced a further significant increase (p < 0.05) in [HCO3]p of 10.8%, to values not significantly different from those in nonbicarbonate-loaded subjects with gastric alkalosis: 33.2 ± 1.2 mEq/1. GFR decreased significantly by 8.4% (from 98 ± 4 to 90 ± 3 ml/min, p < 0.025), offsetting nearly commensurately the increase in [HCO3]p so that total renal bicarbonate reabsorption was not significantly increased (2.90 ± 0.12 vs. 2.97 ± 0.19 mEq/min, p = NS). Thus, in humans ingesting a low NaCl diet, when bicarbonate availability is not rate-limiting, bicarbonate reabsorption appears to be maximal and does not increase in response to gastric aspiration; the increment in [HCO3]p induced by gastric aspiration is perpetuated predominantly by a reductio