Reverse osmosis desalination is increasingly applied to address the global challenge of water scarcity and pollution of available water resources. This study investigates interactions of select organic macromolecules - sodium alginate, humic acid and bovine serum albumin - with the inherent operational limitation of membrane scaling caused by gypsum (CaSO4 center dot 2H(2)O) bulk and surface crystallization. Tailored operation of a bench-scale reverse osmosis system demonstrated that severe concentration polarization provoked gypsum surface crystallization as opposed to bulk crystallization and vice versa. Gypsum bulk crystallization was significantly retarded by coexisting macromolecules. Macromolecular adsorption onto growth sites of crystals appeared to be the underlying mechanism of retardation. Supplemental crystallization experiments were performed to determine the prolongation of gypsum induction times in the presence of macromolecules. Macromolecular properties and concentration as well as crystallization kinetics determined the extent of retardation. Scaling by gypsum surface crystallization, however, was enhanced in the presence of sodium alginate and humic acid. The developed macromolecular fouling layers shifted gypsum scaling mechanisms from bulk to surface crystallization. This was most clearly observed for sodium alginate, which caused strongest membrane fouling. A correlation between the extent of fouling and the enhancement of surface crystallization is suggested. Hence, any potential anti-scale effects exhibited by various organic macromolecules, may be superposed by enhanced concentration polarization due to macromolecular fouling. (C) 2016 Elsevier B.V. All rights reserved.