There is an extensive collagen network in the heart. The precise anatomy and function of this system has not been fully elucidated. The system does appear to contribute to diastolic compliance, and evidence indicates that the system may be important in directing the stress generated by sarcomeres to the ventricular cavity. Little is known about the mechanisms controlling collagen deposition and resorption in the heart. In this paper the authors demonstrate that disulfide reagents are capable of inducing a collagenolytic reaction in the isolated perfused heart that removes all components of the collagen matrix of the heart as visualized by scanning electron microscopy. The expression of collagenolytic activity requires perfusion of the heart for 1 hour with a disulfide reagent followed by 2 hours with Krebs-Hensleit alone. These results suggest that an inducible and active collagenolytic system exists in cardiac tissue and that this system may be expressed under conditions of oxidative stress.