Two simple, accurate and selective methods for the determination of diphenhydramine in pharmaceutical grade sample and in dosage forms are described. The titrimetric method is based on the precipitation of the chloride content of the drug as AgCl with a known excess of silver nitrate and back titration of the residual silver nitrate with thiocyanate using iron(III) as indicator. The reaction stoichiometry and the range of determination have been evaluated. The spectrophotometric method involves the displacement of thiocyanate of mercuric thiocyanate from the ionized chloride and the subsequent reaction of the liberated thiocyanate with iron(III) to form the familiar red colored complex, Fe(SCN)(2+) which is measured spectrophotometrically at 460 nm. The Beer's law is obeyed over the range 4-45 mug mL(-1) of diphenhydramine HCl, the molar absorptivity and Sandell sensitivity being 3.45 x 10(3) L(.)mol(-1) cm(-1) and 84.5 ng cm(2), respectively at 460 nm. The reaction variables have been optimized. The methods have been found to be very simple, cost-effective and reliable for three dosage forms containing diphenhydramine hydrochloride.