Alginate microspheres were prepared by a water-in-oil emulsion solvent diffusion method. The alginate microspheres were post-cross-linked with Ca2+ ions. Influence of Ca2+ concentration on the characteristics and drug release behaviors of alginate microspheres was evaluated. Blue dextran was used as a water-soluble model drug. The non-cross-linked alginate microspheres were less than 100 mu m in size and had a spherical shape. The cross-linked alginate microspheres were also spherical in shape with a rougher surface but their particle sizes were larger than 100 mu m. The drug encapsulation efficiency of the non-cross-linked alginate microspheres was very high (82%). The drug encapsulation efficiency of alginate microspheres cross-linked with 5% and 10% Ca2+ concentrations were similar to the non-cross-linked microspheres. The in vitro drug releases of the cross-linked alginate microspheres showed prolong release profiles. The cumulative release of blue dextran decreased as the Ca2+ concentration increased. Thus, Ca2+-post-cross-linked alginate microspheres show possibility for use as controlled-release drug carriers. (C) 2014 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.