The industrially important application of vanadium phosphorus oxide catalysts is the partial oxidation of n-butane in multi-tubular fixed bed reactors. Despite many decades of investigation about the functionality of the catalyst, the reaction mechanism is still under debate. However, the loss of phosphorus from the catalyst as a technically important phenomenon was until now hardly considered in the scientific literature: this phosphorus loss during long term operation has a strong effect on the temperature distribution in the reactor, which in turn significantly affects the catalyst selectivity. Therefore, technical reactor operation usually requires the addition of ppm levels of an organic phosphorus compound together with water to the reactor feed. For a macro-scale investigation of the phosphorus dynamics, the present study reports elaborated experiments in an industrial scale fixed bed reactor. The experiments revealed significant changes in catalyst activity and reactor performance induced by only minor variations in the feed contents of phosphorus and water as function of butane feed and space velocity, as well as strong interactions between these two additional feed components. These observations are further related to the many literature reports about the active catalyst surface. Common aspects explaining the dynamic catalyst behavior were combined in a new scheme for the VPP/VPO surface chemistry. (C) 2015 Elsevier B.V. All rights reserved.