Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) crosslinked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide (E/N-DSC) towards enzymatic degradation. Contrary to non-cross-linked DSC (N-DSC), which had a rate of weight-loss of 18.1% per hour upon degradation, no weight loss was observed for E/N-DSC during a 24 h degradation period. The tensile strength of the E/N-DSC samples decreased during this time period, resulting in partially degraded samples having 80% of the initial tensile strength remaining. The susceptibility of E/N-DSC samples towards enzymatic degradation could be controlled by varying the degree of cross-linking of the samples. Ethylene oxide sterilization of E/N-DSC samples made the material more resistant against degradation compared with non-sterilized E/N-DSC samples. This may be explained by a decrease of the adsorption of bacterial collagenase onto the collagen owing to reaction of ethylene oxide with remaining free amine groups in the collagen matrix.