An increase in urinary ammonium excretion is an established renal compensatory mechanism to the induction of acidosis in man and a number of experimental animals, including rodents and the dog. In contrast, the poor renal ammoniagenic capacity and the ensuing low urinary buffer capacity is known to contribute to the particular susceptibility of herbivores to a relatively low systemic acid dose. Some 40 years ago, however, it was shown, in experiments involving isotonic sodium phosphate loading of acidotic rabbits, that renal ammoniagenesis could be enhanced resulting in a stimulation of urinary ammonium excretion in this species, thus increasing their capability to unload acid at the renal level, and consequentially improve their acid tolerance. With the view of securing a plausible physiological explanation for this rabbit-unique phenomenon, sodium phosphate loading studies were repeated on anaesthetized, acidotic rabbits (1). It was observed that while the animals were being rendered hyperphosphataemic (7.9 ± 0.1 mmoles.Litre-1 (N = 5) vs 2.1 ± 0.1 mmoles.Litre-1 (N= 10) pre-infusion, (p< 0.001)) and hyperphosphaturic (72 ± 3.8 mmoles.Litre-1 vs 5 ±1mmol.Litre-1 (N=9), pre-infusion, p< 0.001) over an 80 minute isotonic sodium phosphate infusion period, two unrelated sets of urinary ammonium excretion data were obtained. When assayed via an enzymatic validated Berthelot reaction, urinary ammonium excretion was found to increase 1.6 fold (0.08 ± 0.02 µmoles.min-1 vs 0.05 ± 0.01 µmoles.min-1 (N=9) pre-infusion, p< 0.05). In contrast, a formol-titrimetric method of urinary ammonium analysis reported a higher baseline of urinary ammonium output, in addition to a 2.6 fold increase in ammonium excretion (2.33 ± 0.19 µmoles.min-1 vs 0.9 ± 0.09 µmoles.min-1 (N=11) pre-infusion, p≤ 0.001). Values are means ± S.D., significant difference being determined by student t-test. An investigation of the discrepancy between the two assays revealed a particular susceptibility of the formol titration procedure of urinary ammonium analysis to phosphate interference (2), thus yielding exaggerated estimations of urinary ammonium, and casting doubt on the relative significance of phosphate as an in vivo stimulant of ammonium output in the acidotic, hyperphosphataemic rabbit. Rather it would appear from additional measurements done in this laboratory (3) that phosphate infusion increases acid unloading in the acidotic rabbit primarily through the mechanism of increased titratable acid excretion. The physiological relevance of the minuscule though significant increase in urinary ammonium excretion, that was observed following phosphate infusion in the acidotic rabbit, must be of minimal significance, considering that pharmacological quantities of phosphate were used. Furthermore, the use of phosphate infusion as a protocol to treat acidosis in humans is limited, because of the toxic consequences of elevated plasma phosphate levels following sodium phosphate infusion.