The substution reaction of poly(vinyl chloride) (PVC) with sodium thiobenzoate has been performed in two series of solvents differing in molecular structure. One series includes cyclohexanone and the other includes more basic solvents, such as N-methylpyrrolidone and N,N-dimethylformamide. The evolution of unreacted iso-, hetero- and syndiotactic triad contents with degree of substitution has been followed by C-13 NMR spectroscopy. In the former type of solvent, the mm located at the end of long isotactic sequences react exclusively. Then, the heterotactic triad mr is involved in the reaction. The latter type of solvent does not discriminate between either structure from the outset of the reaction, as is the case for the former group of solvents at conversions higher than roughly 7%. Only a small fraction of mmr tetrads reacts occasionally by the central chlorine of its mr triad instead of the mm. Through the foregoing results, the mechanisms of substitution, as proposed in a previous work, have been confirmed to be independent of the type of solvent utilized. The approach to the local configurational nature of the mechanisms is discussed on the grounds of the FTIR results. The same reaction has also been studied in aqueous suspension in the presence of a phase-transfer catalyst. In this experimental system, the behaviour of the modified samples in relation to the evolution of the content of mmr and rrmr structures rather approximates to that obtained for basic solvents. On the whole, the results, as analysed in the light of earlier work, provide some novel ideas on the role of the tacticity-dependent microstructure and the related local conformations in the chemical reactions of PVC.