High-throughput in vitro refolding of disulfide-bond-containing proteins is particularly challenging because their aggregation competes with their refolding rate (to form inclusion bodies).Refolding techniques of such therapeutically-relevant proteins are further impeded by the absence of effective methods for the detection of their native forms among numerous non-native isomers and partially folded intermediates.We demonstrate a method which combines top-down mass spectrometry with a mildly-reductive redox pulse to identify the native form of multi-disulfide-bond-containing proteins even when present in a mixture of other such proteins.Our method requires no prior experimentation/optimization,knowledge of proteins physicochemical characteristics or function/activity,is amenable to automation and scale-up and therefore,effectively fulfils criteria for structural genomics/proteomics applications.