Macromolecularly imprinted calcium phosphate/alginate hybrid polymer microspheres surface imprinted with bovine serum albumin were prepared in inverse-phase suspension by introducing the intermixture solutions of bovine serum albumin (BSA) and CaCl2 in sodium alginate aqueous solution where (NH4)(2)HPO4 was added beforehand. Morphology of the imprinted microspheres was observed by optical microscopy. Rebinding dynamic and thermodynamic behaviors of surface molecularly imprinted calcium phosphate/alginate polymer microspheres (CP/A SMIPMs) and embedding molecularly imprinted calcium phosphate/alginate polymer microspheres (CP/A EMIPMs) were evaluated. CP/A SMIPMs exhibited significant improvement in equilibrium rebinding capacity (Q(e)) and imprinting efficiency (IE), compared to CP/A EMIPMs. The surface of CP/A SMIPMs was more competent to facilitate the migration and re-assembling of proteins. Surface specific peak and interior specific peak were proposed to describe the characteristics of surface and interior specific rebinding behaviors in rebinding dynamics. The effects of (NH4)(2)HPO4 addition were investigated in detail, along with the concentration of sodium alginate and CaCl2 solutions to the rebinding and imprinting property of imprinted microspheres. (c) 2008 Wiley Periodicals, Inc.