1. Single skeletal muscle fibres of Xenopus laevis were used to investigate the involvement of a mechano-sensitive link in excitation-contraction coupling (EC coupling). 2. Fibres were stimulated by intermittent tetani until tension fell to about 40% of its initial level. Fibres were then stressed either by briefly stretching the fibres to 120% of their resting length or by exposing them to hypotonic Ringer solution ([NaCl] reduced to 80%) for 5 min. 3. In six of thirty-five stretched fibres and in all fourteen fibres exposed to hypotonic solution, a long-lasting depression of tension ensued. Tetanic tension then recovered slowly, often taking more than 10 h to return to its initial level. 4. During the period of minimal tension production, 12 mM caffeine induced a maximum contracture; 190 mM K+ induced a contracture larger than previous or subsequent tetani, and perchlorate (1 mM) slightly augmented tetanic tension. 5. Neither protease inhibitors nor a protein synthesis inhibitor altered the long-lasting period of tension depression and slow recovery. A free-radical scavenger was also without effect. 6. It is concluded that there is a mechano-sensitive link involved in EC coupling which can be damaged easily in fatigued muscle fibres.