Spider egg sac silk (SpESS) were enzymatically cleaned and their biodegradation in vivo and in vitro, as well as their biocompatibility were studied. Proteinase K treatment diminished the tenacity and the strain of the SpESS fibers in proportion to the enzyme concentration. Fibers treated with trypsin were not significantly affected. Tensile properties of Vicryl, SpESS and of silkworm (Bombyx mori) silk fibers (SWS) were measured after incubation in phosphate buffered saline (PBS) at 37 degrees C up to 12 weeks. Biodegradation of SpESS and SWS was insignificant compared to Vicryl. Five milligram SpESS fibers from laboratory grown spiders (Araneus diadematus) were treated with proteinases before sterilization and subcutaneously implanted in Wistar rats. After 1, 4 and 7 weeks the immunological reaction was compared to untreated SpESS and polyglactin (Vicryl) control samples. SpESS samples treated with trypsin only or in combination with a Proteinase K treatment induced less inflammatory reactions than untreated silk fibers. The enzymatical cleaning could diminish the tensile properties, but enhanced the biocompatibility of the SpESS fibers rendering them appropriate for use in biomaterial application where the slow biodegradability is an advantage.