The controlled formation of intramolecular disulfide bridges in peptides, while avoiding unwanted oligomerization, is a significant challenge. Ellman＇s reagent, 5,5＇-dithiobis(2-nitrobenzoic acid), was developed originally in the context of an assay for measuring free thiol concentration under physiological conditions. The present studies demonstrate that this reagent, when bound through two sites to a suitable solid support (PEG-PS, modified Sephadex, or controlled-pore glass), is an effective mild oxidizing reagent that promotes the formation of disulfide bridges. Rates and yields of the reactions were determined as a function of pH, excess of oxidizing reagent, resin loading, and parent support, for the preparation of oxytocin and deamino-oxytocin (9 residues, disulfide bridge between residues 1 and 6), somatostatin (14 residues, disulfide bridge between residues 3 and 14), alpha-conotoxin SI (13 residues, disulfide bridges between residues 2 and 7; 3 and 13), and apamin (18 residues, disulfide bridges between residues 1 and 1 1; 3 and 5). Cystine dimers of these peptide models formed, if at all, in relatively low amounts. Use of solid-phase Ellman＇s reagents to oxidize the linear precursors of conotoxin or apamin (tetrathiols) gave as the main products the correctly paired regioisomers. Particular advantages of the overall approach include fast reaction rates over a wide range of pH, from 2.7 to 6.6; easy purification of disulfide-containing products; and the specificity and reusability of the reagents.