The applicability of a PALL tangential flow filtration (TFF) system for size fractionation of natural dissolved organic matter was investigated. The performance of polyethersulfone membranes with nominal molecular weight cut-off of 1 kDa, 5 kDa and 50 kDa was examined for isolation of low and high molecular weight compounds in fresh and estuarine waters with diverse physicochemical properties. Detailed protocols for operating the TFF- system and for membrane cleaning are proposed. The ultrafiltration membranes can be efficiently cleaned to provide low carbon blanks (