Disruption to proteins within the myofiber after a single bout of unaccustomed eccentric exercise is hypothesized to induce delayed onset of muscle soreness and to be associated with an activation of satellite cells. This has been shown in animal models using electrical stimulation but not in humans using voluntary exercise. Untrained males (n=8, range 22-27 yrs) performed 210 maximum eccentric contractions with each leg on an isokinetic dynamometer; voluntarily (VOL) with one leg and electrically induced (ES) with the other leg. Assessments from the skeletal muscle were obtained prior to exercise and at 5, 24, 96 and 192 hr post-exercise. Muscle tenderness rose in VOL and ES after 24 hr, and did not differ between groups. Maximal isometric contraction strength, rate of force development and impulse declined in the VOL leg from 4 hr after exercise, but not in ES (except at 24 hr). In contrast, a significant disruption in cytoskeletal proteins (desmin) and a rise in myogenic growth factors (myogenin) occurred only in ES. Intracellular disruption and destroyed Z-lines were markedly more pronounced in ES (40%) compared to VOL (10%). Likewise, the increase in satellite cell markers (neural cell adhesion molecule (N-CAM) and Pax-7) was more pronounced in ES vs VOL. Finally, staining of the intramuscular connective tissue (tenascin C) was increased equally in ES and VOL after exercise. The present study demonstrates that in human muscle, the delayed onset of muscle soreness was not significantly different between the two treatments despite marked alterations in intramuscular histological markers, particularly, myofibre proteins and satellite cell markers. An increase in tenascin C expression in the mid belly of the skeletal muscle in both legs, provides further evidence of a potential role for the extracellular matrix in the delayed onset of muscle soreness phenomenon.