Sensitive methods were developed for the determination of two sulfhydryl containing drugs namely acetylcysteine (I) and captopril (II). The methods were based on reacting the drugs with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in the presence of sodium tetraborate in absolute methanol. The yellow colored products obtained were measured spectrophotometrically at 417 and 420 nm for (I) and (II), respectively and by differential pulse polarography at -872 and -1007 mV (vs. Ag/AgCl electrode) for compounds (I) and (II) after getting rid of excess unused reagent by extraction with ether. The different experimental parameters were studied and optimized spectrophotometrically. The proposed methods were validated and applied to the determination of the cited drugs in their pharmaceutical preparations. The results were statistically analyzed and compared to those of a reference HPLC method.