Poly　vinyl　acetate　grafted　calcium　alginate　hydrogel　microspheres　were　prepared　with　bovine　serum　albumin　(BSA)　as　molecular　template.　The　microspheres　exhibited　homogeneous　and　core-shell　structure　according　to　different　preparation　strategy.　The　rebinding　and　swelling　property　of　microspheres　showed　responsiveness　toward　ionic　strength,　temperature,　and　pH.　It　was　found　the　highest　separation　factor　of　1.85　and　imprinting　efficiency　of　1.75　when　the　Ca2+　ionic　strength　was　1.25　and　0.34　mol/kg,　respectively.　The　separation　factor　was　found　decreased　as　temperature　grew　from　29　to　45　degrees　C　while　the　imprinting　efficiency　reached　a　peak　value　at　about　37　degrees　C.　Separation　factor　of　BSA　imprinted　microspheres　at　different　pH　was　also　recorded　and　two　peaks　were　found,　which　were　considered　to　be　caused　by　the　similar　swollen　state　due　to　ionic　and　covalent　crosslinking　structure　of　modified　microspheres.　The　recognition　responsiveness　is　suggested　to　be　influenced　by　environmental　effects　due　to　the　changing　in　imprints＇　configuration　at　different　swollen　states.　(c)　2012　Wiley　Periodicals,　Inc.　J.　Appl.　Polym.　Sci.,　2013