The role of chemical and physical interactions in cleaning of organic-fouled reverse osmosis (RO) membranes is systematically investigated. Fouling and cleaning experiments were performed with organic foulants (alginate and natural organic matter) that simulate effluent organic matter (EfOM) and selected cleaning agents using a laboratory-scale crossflow test unit. Following accelerated organic fouling runs with divalent calcium ions, cleaning experiments were performed at various chemical and physical conditions. The results showed that a metal chelating agent (EDTA) and an anionic surfactant (SDS) were able to clean the fouled RO membrane effectively by optimizing chemical (dose and pH) and physical (time, crossflow velocity, and temperature) conditions during cleaning. The permeate flux was, however, poorly recovered when cleaning was performed with NaOH (pH 11). Interfacial force measurements (by AFM) further confirmed the cleaning results, demonstrating the influence of cleaning agents on reducing the foulant-foulant adhesion force. The results showed that the adhesion force caused by calcium-induced foulant-foulant interaction was reduced significantly with EDTA and SDS cleaning, while substantial adhesion force still remained following NaOH cleaning. It is proposed that an efficient cleaning agent and favorable cleaning conditions could be selected by considering two important mechanisms: chemical reaction between cleaning agents and foulants in the fouling layer, and mass transfer of chemical agents (from the bulk phase to the fouling layer) and foulants (from the fouling layer to the bulk phase). (c) 2005 Elsevier B.V. All rights reserved.