The influence of both low and high molecular weight compounds present in red grape must in the decline of permeate flux (J(v)) during its nanofiltration was studied. The most important low molecular weight compounds are glucose and fructose while other compounds, such as polyphenols, polysaccharides, proteins etc. have high molecular weight. A synthetic solution containing the typical low molecular weight compounds of natural must was nanofiltered and the results compared with those obtained by the nanofiltration of commercial red must. During nanofiltration of red must a gel layer was formed and thickened on the membrane surface leading to a rapid decrease in J(v) and a slow increase of the concentration of sugars in the retentate due to the small permeate volume recovery. A method was proposed to allow studying individually the resistances and fouling mechanism generated by sugars and high molecular weight solutes under these extreme conditions. Results showed that high molecular weight compounds have more influence on the permeate flux decrease since they are mainly responsible for the fouling phenomenon (cake filtration fouling mechanism), while low molecular weight compounds contribute to the flux decay mostly through an increase of the osmotic pressure during the process. (C) 2012 Elsevier B.V. All rights reserved.