Muscles subjected to eccentric exercise, in which the contracting muscle is forcibly lengthened, become sore the next day (delayed onset muscle soreness). In subjects who had their triceps surae of 1 leg exercised eccentrically by walking backwards on an inclined moving treadmill, mapping the muscle 48 hours later with a calibrated probe showed sensitive areas were localized but not restricted to the muscle-tendon junction. Injection of 5% sodium chloride into a sensitive site in the exercised leg did not produce more pain than injections into the unexercised leg, suggesting that nociceptor sensitization was not responsible. Applying controlled indentations to a sensitive area showed that the pain could be exacerbated by 20-Hz or 80-Hz vibration. In an unexercised muscle, vibration had the opposite effect; it reduced pain. Pain thresholds were measured before, during, and after a pressure block of the sciatic nerve. The block affected only large-diameter nerve fibers, as evidenced by disappearance of the H reflex and a weakened voluntary contraction, leaving painful heat and cold sensations unaltered. Pain thresholds increased significantly during the block. It is concluded that muscle mechanoreceptors, including muscle spindles, contribute to the soreness after eccentric exercise.