We examined the effect of some crude snake venoms, isolated toxins and non-specific cytotoxic agents on isolated extensor digitorum longus (EDL) and soleus (SOL) muscles of the mouse. The muscles were continuously perfused with a physiological saline solution. Crude venoms from Crotalus viridis viridis, Agkistrodon contortrix lacticinctus and Notechis scutatus scutatus were tested at a concentration of 25-50 mu g ml(-1). The increase in the rate of creatine kinase (CK) release (above basal levels) induced in each muscle by each venom or toxin was measured. Also, the myotoxic effect of these agents was investigated with the light microscope. EDL and SOL had the same range of basal rate of CK release (0.30 +/- 0.06 U g(-1) hr(-1), N = 26), weight (7-10 mg) and content of CK (717.18 +/- 80.19 U g(-1) and 501.00 +/- 62.28 U g(-1), N = 8), but they had a different sensitivity to the myotoxic action of the tested venoms. The rate of CK release in EDL muscles was in the range of 24-60 U g(-1) hr(-1) after 60 mill of exposure to 35 mu g ml(-1) of each crude venom, whereas the increase of rate of CK release in the SOL was in the range of 1.5-4.0 U g(-1) hr(-1). Crotoxin and myotoxin a (10 and 25 mu g ml(-1), respectively) were also more effective in EDL than in SOL muscles. The non-specific cytotoxic agents Triton X-100 (0.01%) and polylysine(100 mu g ml(-1)) induced the same increase of rate of CK release in both muscles. The data presented in this article show that isolated murine EDL muscles are more sensitive than SOL to the myotoxic action of some snake venoms and toxins. Copyright (C) 1996 Elsevier Science Ltd