Fibroin, the core of the silk filament protein, has been proposed as a biomaterial for different biomedical applications since it can be engineered as a thread, fabric or film. Infrared spectroscopy suggests that the dissolution of the fibroin filaments and subsequent casting of the fibroin solution into films followed by treatment with methanol alters the protein structure leading to an increase in amorphous domains. The adsorption ofserum proteins on fabrics and films showed different hydrophobic binding strengths for the two materials with the protein binding being greatest for the more hydrophobic fibroin fibers. Differences between the materials were also observed in the adsorption of key immunoproteins. Although the C3 fragment of the complement system was adsorbed on both the surfaces, it appeared to be activated preferentially on the fibroin films and not on the fibroin fibers, whereas the Bb and C1q factors were only significantly present on the fibroin fabric. IgG appeared to be adsorbed, although to different extents, on both types of fibroin substrates. These results suggest that the biocompatibility of the silk fibroin may be affected by changes in protein structure induced by processing the material.