To develop a clear understanding of the biochemical mechanism of muscle degeneration and regeneration induced by a single dose of Notechis scutatus scutatus venom, we have correlated changes in the levels of a series of muscle structural proteins and proteolytic enzymes. The degradation of structural proteins post-injection fell into two broad groups; those completely degraded within 3-6 hr (e.g. C- and M-proteins, skelemin), and within 1-2 days (e.g. myosin, actin, troponin), respectively. Similarly, activation of proteases followed two general patterns; those enzymes showing substantially increased activity after 12-24 hr (lysosomal cathepsins, leucyl aminopeptidase) and those enzymes showing decreased activity after 12-24 hr, with substantially increased activity after 3-4 days (mainly cytoplasmic proteases). The data suggest that activation of cathepsins B, L and D and in particular leucyl aminopeptidase, may be responsible for the early stages of structural protein catabolism, and are thus potential therapeutic targets to prevent myonecrosis following envenomation.