O,S-Dialkyl phenylphosphonothioates (5a-d) are good simulants for the nerve agent VX in nucleophilic substitution reactions. Hydrolyses of 5a-d in 0.1 M aqueous NaOH occur with half-lives of 4-18 min and with the formation of both P-S and P-O cleavage products, 6a-d and 7a-d, respectively. Reactions of these substrates with o-iodosobenzoate (IBA), however, are chemospecific at P-S. For example, in 0.05 M micellar cetyltrimethylammonium chloride (CTACl) at pH 9.5 (pD 9.9) in D2O, 0.063 M IBA cleaved 0.02 M 5a (to 6a) with k = 0.115 min(-1), t(1/2) similar to 6 min. The second-order rate constant for this reaction in 0.1 M CTACl solution was similar to 1.9 M(-1) min(-1).