Difference spectroscopy is a technique by which we can observe the changes in absorbance of a chromophore that has been perturbed by another molecule. This is readily achieved experimentally using a doublebeam spectrophotometer in which the reference and sample compartments contain the same concentration (and path length) for the chromophore, but with perturbant added to the sample side. The problem is more complicated, however, when both chromophore and perturbant absorb in the spectroscopic region of interest. To compensate for this complication, the "tandem cell" technique, with two pairs of matched cuvets, of Herskovits and Laskowski (1) is generally used. This technique has the disadvantage that highly accurate small-volume additions must be made and at least two of the four cuvets must be precisely matched with respect to path length. A lesser known technique was proposed by Yankeelov (2) in which a special cell was designed that eliminated the need for precise small-volume additions. It occurred to us that a modification of these methods could simplify the procedure, make the technique more accurate, and even obviate the need for expensive specially designed or matched cuvets.