Eccentric muscle actions are associated with ultrastructural changes. The severity and types of change depend on the nature of the stimulation protocol, and on the method for assessing such changes, and can be regarded as a continuum from mild changes to pathological-like changes. Most studies describing more severe changes have been performed on animals and only a few in humans, some using electrical stimuli. Hence, a debate has emerged on whether voluntary actions are associated with the pathological-like end of the continuum. The aim of this study was to determine whether severe muscle damage, i.e., extensive ultrastructural changes, is confined to animal studies and studies on humans using electrical stimuli. Second, because there is no generally approved method to quantify the degree of muscle damage, we compared two published methods, analyzing the Z disks or sarcomeres, as well as novel analyses of pathological-like changes. A group of untrained subjects performed 70 voluntary maximal eccentric muscle actions using the elbow flexors. On the basis of large reductions in maximal force-generating capacity (on average, -62 +/- 3% immediately after exercise, and -35 +/- 6% 9 days later), five subjects were selected for further analysis. Biopsies were taken from m. biceps brachii in both the exercised and nonexercised arm. In exercised muscle, more disrupted (13 +/- 4 vs. 3 +/- 3%) and destroyed (15 +/- 6 vs. 0%) Z disks were found compared with nonexercised muscle. A significant proportion of exercised myofibers had focal (85 +/- 5 vs. 11 +/- 7%), moderate (65 +/- 7 vs. 11 +/- 6%), and extreme (38 +/- 9 vs. 0%) myofibrillar disruptions. Hypercontracted myofibrils, autophagic vacuoles, granular areas, central nuclei, and necrotic fiber segments were found to various degrees. The present study demonstrates that the more severe end of the continuum of ultrastructural changes occurs in humans after voluntary exercise when maximal eccentric muscle actions are involved.