The aim of this research was to establish a rationale for the cleaning of reverse osmosis (RO) membranes fouled by whey. Whey was processed using a hydrophilic polyamide FT30 RO membrane. The effects of operating conditions such as transmembrane pressure, temperature and cross-flow velocity on flux behavior were elucidated before studying the cleaning. A wide variety of cleaning agents including acids, bases, enzymes and complexing agents was used. Resistance removal and flux recovery were used for demonstrating the cleaning efficiency. Hydrochloric acid (0.05 w%) resulted in maximum flux recovery and complete resistance removal. Although sodium hydroxide showed high cleaning efficiency, it may damage the membrane, predominantly at a high pH. Nitric acid and ammonia showed high but not complete resistant removal. Other acids (phosphoric acid and oxalic acid), ammonium chloride, urea and surfactants (SDS, Triton-X100 and CTAB) exhibited moderate effects while EDTA was of low efficiency. The cleaning effectiveness depends on the cleaner concentration. Using sulphuric acid, higher concentration caused lower resistance removal. For HCl the cleaning efficiency increased with the cleaner concentration, passed a maximum and decreased afterwards. Operating conditions such as cleaning time and temperature affect cleaning efficacy. A longer time and higher temperature provide higher resistance removal. However, the effects are somewhat limited.