An isotope dilution assay for racemization during acid couplings is described and applied to carbodiimide-mediated synthesis. Using the coupling of t-BOC-L-phenylalamine with glycine derivatives as a model, racemization in solution falls in the 0.01 to 0.1% range and it is a function of reagent concentrations. A typical coupling using the solid phase method shows 0.03% racemate.