In this study, single and multi-metal ion-exchange systems, Na+/H+/Cd2+, Ne+/H+/Pb2+, Na+/H+/Cu2+, Na+/ H+/Zn2+ and Na+/H+/Cd2+/Pb2+/Cu2+/Zn2+, were studied in continuous mode using a fixed-bed column packed with Na-loaded macroalgae Pelvetia canaliculata as natural cation exchanger. Breakthrough curves were obtained for all the systems operating at inlet metal concentrations of 20 mg/L. For the single metal ion-exchange systems, the service capacity obtained was 329, 107, 120 and 184 bed volumes for Zn2+, Cu2+, Cd2+ and Pb2+, respectively. Desorption, using 0.1 M HNO3 as eluent, was fast and near to 100% of effectiveness, using only 10 bed volumes of eluent, achieving maximum metal concentrations at the column outlet of 2.8 3.8, 1.5 and 1.8 g/L for Cd2+, Pb2+, Cu2+ and Zn2+ ions, respectively. In the multi-metal sorption process, Cd and Zn break through the column faster than Cu and Pb due to its lower affinity for the biosorbent. An overshoot in the Cd and Zn outlet concentrations was observed for the multi-metal system and explained by the competitive uptake with Pb and Cu ions. Biosorption of Cd2+, Pb2+, Cu2+ and Zn2+ by P. canaliculata pre-loaded with sodium is based on an ion-exchange mechanism accompanied by the release of Na+ into the liquid phase. A mass transfer model, including the mass balances to the packed bed column and thin plate algal particles, assuming a LDF model, and complementary equations (as mass action law equilibrium relations, initial and boundary equations), was able to fit well the experimental data. Finally, an ion-exchange pilot plant was tested for the treatment of a multi-metal synthetic solution using the natural macroalgae. (C) 2015 Elsevier B.V. All rights reserved.