Skeletal muscle regeneration was studied following injections of Bothrops asper venom and a myotoxin isolated from the crude venom. In toxin-injected muscle regeneration proceeded normally. By 4 days there were myotubes and small regenerating cells. The size of the cells increased by 1 and 2 weeks, and by 4 weeks regenerating cells were fully developed. The regenerated cells retained centrally located nuclei. The regenerative process in venom-injected muscle was not completely normal--by 1 and 2 weeks four main areas, based on the predominant cell type present, were observed in the tissue: (a) necrotic muscle cells; (b) regenerating muscle cells; (c) fibroblasts and collagen; (d) adipocytes. Furthermore, some nerve fibers were demyelinated. Samples obtained 4 weeks after venom injection showed an almost complete regeneration in many areas, whereas in other areas nests of small regenerating cells were surrounded by portions of adipose tissue and collagen. At four weeks regenerating cells in venom-injected muscle were significantly smaller than cells in toxin-injected and saline-injected muscles. There was a significant reduction in capillary/muscle cell ratio in areas of the muscle where hemorrhage and myonecrosis were present 30 min after injection of B. asper venom. Since B. asper venom drastically affects the microvasculature, it is proposed that impairment of regeneration after injection of crude venom is a consequence of diminished blood supply to some areas of the muscle.