Microencapsulation of cells is a promising approach to prevent rejection in the absence of immunosuppression. Clinical application, however, is hampered by insufficient insight in factors influencing biocompatibility of the capsules in humans. In the present study we exposed alginate-based capsules prepared of different types of alginate to human peritoneal fluid. Subsequently we studied the physicochemical changes of the capsule's surface by applying micro-Fourier Transform Infrared Spectroscopy. We did test alginate-beads and alginate-poly-L-lysine capsules prepared of different types of alginate. In all tested capsule formulations we found adsorption of components from human peritoneal fluid and clear physicochemical changes of the surface. These changes were alginate-dependent. The adsorption had no significant effects on the permselective properties of the capsule but we found a strong increase of TNFα production by human peripheral blood mononuclear cells when exposed to alginate-beads treated with human peritoneal fluid. This elevated responsiveness was not observed with alginate-PLL capsules. The results show that alginate-based capsule surfaces always undergo physicochemical changes of the surface when exposed to human peritoneal fluid. This adsorption may lead to enhancement of the inflammatory responses against the microcapsules. Our result implicate that biocompatibility measurements should not only been done with freshly prepared capsules but also with capsules that have been exposed to fluid from the implantation site in order to predict the in vivo responses.