Buffering of "metabolic" acid in tissues other than blood correlates closely with a change in extracellular bicarbonate concentration rather than with a change in extracellular pH. Of particular importance is the evidence for an absence of relation to change in pH. Questions are raised with respect to buffering mechanism, but simplification is offered for diagnosis. A clearer focus can be given to the guidepost changes in Pco₂ and bicarbonate concentration. Basic relationships of buffering in the whole body are reviewed, and a modified diagnostic rationale is offered, based on a two- rather then a three-dimensional analysis. AM. J. PHYSIOL. 277 (ADV. PHYSIOL. EDUC. 22): S136-S139, 1999.