1. The involvement of extracellular calcium in experimental muscle damage has been studied in an isolated mouse soleus muscle preparation. 2. The enzyme efflux and ultrastructural damage seen after excessive contractile activity were markedly reduced when the extracellular calcium was withdrawn. Low extracellular calcium also protected against the large enzyme efflux seen after treatment with low concentrations of detergent. 3. Treatment of the muscle with the calcium ionophore A 23187 caused significant release of enzyme from the muscle. 4. Nifedipine did not prevent the enzyme release after stimulation and although in some circumstances verapamil appeared to have some protective effect this was probably due to a local anaesthetic action on the muscle and not to any specific effect on calcium movement. 5. It is concluded that extracellular calcium is important in mediating at least the two forms of muscle damage studied here.