Pain, stiffness, and indicators of muscle damage occur at different times after eccentric muscle action. After a single bout of maximal resisted lengthening of the elbow flexors, elbow position, pain perception, and indicators of cellular damage were measured. Immediately postexercise, a significant decrease in resting muscle length was observed that continued to 48 h. At this time, an increase in perceived muscle soreness was noted (P less than 0.05), and a biopsy of the biceps brachii revealed mast cell degranulation, separations of the extracellular matrix from myofibers, and increased plasma constituents in the extracellular space. It is proposed that myofiber disruption allows intracellular proteins to escape and extracellular proteins and ions to enter, causing swelling, whereas the disrupted extracellular matrix initiates the inflammatory response, which includes the release of mast cell granules seen at 48 h postexercise. Thus the delayed sensation of pain (soreness) after repeated eccentric muscle actions probably results from inflammation in response to extracellular matrix disruption.