We report herein the unusual case of a 55-year-old woman who developed a severe systemic allergy to Avitene (microfibrillar collagen hydrochloride), a xenogeneic agent sometimes used for topical hemostasis in laparoscopic cholecystectomy. The patient developed fever, general fatigue, mild liver dysfunction, and prominent eosinophilia postoperatively. A skin allergy test confirmed that these abnormal findings were attributable to an allergic reaction to Avitene.