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The objectives of this study were to determine the effects of solution chemistry on chemical cleaning of nanofiltration (NF) membranes fouled by natural organic matter (NOM) and to evaluate the efficiencies of common chemical cleaning agents. Membrane filtration experiments were conducted under various solution conditions using Suwannee River humic acid (SRHA) and Suwannee River natural organic matter (SRNOM) as the model NOM foulants. To study NOM fouling and chemical cleaning in the presence of colloidal foulants, silica colloids of different particle sizes were used in some experiments. Two types of NF membranes with different surface properties, NF 270 and NF 90, were tested. Ionic strengths ranged from 10 to 100 mM and Ca<sup>2+</sup> and Mg<sup>2+</sup> were used to study the effect of divalent cations. Four model chemical cleaning agents: deionized water, basic solution (NaOH), a metal chelating agent (ethylenediaminetetraacetic acid, EDTA), and an anionic surfactant (sodium dodecyl sulfate) were evaluated. Fouling/chemical cleaning experiments were conducted in a bench-scale continuous-flow dead-end filtration system. The effectiveness of chemical cleaning was assessed based on the permeate flux recovery following the chemical cleaning. For feed stream containing only NOM foulants, the presence of Ca<sup>2+</sup> tremendously enhanced the fouling process, but the membrane flux behavior in the presence of Mg<sup>2+</sup> was similar to that when only monovalent cations, i.e., Na<sup>2+</sup> was present. Includes figures.