This work describes the methodology for the analysis of terfenadine and the acid metabolite of terfenadine in plasma using high-performance liquid chromatography. The use of solid-phase extraction allows the use of robotic or manual sample preparation for the efficient clean-up of terfenadine and terfenadine acid metabolite from plasma. Additional selectivity is obtained through the use of fluorescence detection. For terfenadine, the validated quantitation range of this method is 10.0-84.2 ng/ml with coefficients of variation of 5.7-30%. For terfenadine acid metabolite, the validated quantitation range of this method is 8.2-500 ng/ml with coefficients of variation of 4.1-24%.