The rational development of a stability-indicating assay for nafimidone [1-(2-naphthoylmethyl)imidazole hydrochloride] is demonstrated. It allows resolution of the decomposition products, obtained both on melting and resulting from decomposition in solution. Ion-pair chromatography was used to elute the solution decomposition products before the parent compound, thus producing maximum sensitivity of detection of these in the presence of undecomposed reactant. Stability data in terms of first-order rate constants were obtained in two different buffer solutions both from conventional integrated-rate equations using reactant concentration measurements, and by the initial rate method using decomposition product concentrations. In the light of this investigation, additional criteria for stability-indicating assays are suggested, which exploit the sensitivity as well as specificity of high-performance liquid chromatography.