On exposure (E) of frog semitendinosus muscle to 400 mmol/l urea (U) in sodium chloride Ringer's solution, the tension development to isoK+ solutions decreased, while in choline chloride Ringer it increased. On quick removal (R) of urea, always a block of excitation-contraction (E-C) coupling occurred accompanied by transient or persistent swelling of fibres and a similar but definite decrease of their resting membrane potential (Fig. 2). Muscle contraction could be elicited by caffeine even after UER-treatment but then only the slow tension increase (second phase of normal caffeine contraction) occurred (Fig. 3a). The fast tension increase to caffeine (first phase) could be restored if after UER-treatment 5 mmol/l mannitol (Fig. 3b), a 20 min treatment with choline chloride (Fig. 4a) or sodium isethionate (Fig. 4b) Ringer's solution of double osmolarity were applied. Caffeine contraction could not be elicited when sodium chloride Ringer's solution of double osmolarity was used under similar conditions (Fig. 5). E-C block to isoK+ solution persisted in all these experiments. E-C coupling could partially be restored by short treatment of muscle with caffeine (Figs 6a, b).