The effects of single and combined fouling by sodium alginate, latex and Al2O3 on membrane performance in terms of permeate flux, salt rejection and rejection of the pharmaceutical carbamazepine were evaluated in a laboratory-scale cross-flow filtration unit. Fouling resulted in different extents in permeate flux, salt rejection and carbamazepine rejection over time Combined fouling resulted in larger flux declines, and the influence of Ca2+ addition on flux was pronounced. In contrast, the influence of combined fouling and Ca2+ addition on salt and carbamazepine rejection was limited. Several hypotheses were tested to assess the influence of fouling on carbamazepine rejection. Relating observed rejection results to the solution-diffusion model revealed insight in whether the effect of fouling on rejection was mainly flux-driven or not For most foulants, rejection declined less than what was predicted as a function of flux by the solution -diffusion model, indicating that CECP is not the main mechanism responsible for the decline in rejection upon fouling, especially not for latex fouling layers (regardless of the presence of Ca2+). This was corroborated by CECP modelling data. Solute membrane interaction energies revealed that carbamazepine had higher affinity for the foulants than for the clean membrane surface. As such, it could be hypothesised that for most fouling layers, the relatively small decrease in carbamazepine rejection was mainly due to the decline in flux and the formation of a dense fouling layer on the membrane surface, which had some rejection properties. (C) 2014 Elsevier By. All rights reserved.