The nucleophilic substitution reaction on poly(vinyl chloride) (PVC) with sodium benzenethiolate has been studied in the melt state in the presence of the interacting agents: di-(2-ethylhexyl) phthalate, poly(ϵ-caprolactone), poly(ethylene adipate), poly(ethylene oxide), poly(ethylene glycol) and butyl stearate. The aim was that of viewing whether or not the local chain configuration based mechanism of reaction, as extensively investigated for the same reaction in solution, is a general behaviour and it applies to reaction conditions close to those of the polymer processing. The presence of one interacting agent proves to be necessary for the reaction to exceed 1% conversion. With all the agents the kinetic curves attain a plateau after a rather fast reaction period is elapsed. The reaction yield is found to depend on the agent nature and is not influenced by the amount of agent, which, on the other hand, governs the kinetics. The evolution of isotactic (mm), heterotactic (mr) and syndiotactic (rr) triad contents with degree of substitution for every interacting agent has been followed by 13C NMR. Comparing the results obtained herein and those previously obtained in solution and in heterogeneous phase, two conclusions may be drawn straightforwardly: one is that the reaction proceeds by the mm or the rm triads at the end of isotactic or syndiotactic sequences respectively, i.e. by the mmr or rrmr local structures, the former being much more reactive than the latter; the other is that this mechanism is independent of the reaction conditions utilized. In contrast the superiority of mmr relative to rrmr in reacting strongly depends on the ability of the interacting agent to make the mmr adopt the highly reactive GTTG-TT conformation. A short overview of this stereospecific mechanism and of its implications is given.