Using the sucrose vaseline gap technique, experiments were carried out on isolated frog twitch muscle fibre to investigate the role of chloride ions in excitation-contraction coupling. In current clamp conditions, replacement of chloride ions by impermeant anions led to an increase of the amplitude of the early after potential and of the amplitude of the twitch. Addition of a chloride channel blocker, anthracene-9-carboxylic acid gave similar results. In voltage clamp conditions, replacement of chloride ions by impermeant anions induced a decrease of the outward current and an increase of both the amplitude of the contraction and of the resting tension. Addition of anthracene-9-carboxylic acid gave similar results except that resting tension was not modified. Replacement of chloride ions by impermeant anions resulted in a shift of the tension-voltage relationship toward negative potentials and in an increase of the amplitude of the contraction at all potentials. Outward currents were also reduced at all potentials but no shift of the current-voltage relationship was observed. Similar results were obtained upon addition of anthracene-9-carboxylic acid. Rapid filtration experiments were performed on isolated sarcoplasmic reticulum vesicles to study the role of chloride ions in Ca2+ release. Under conditions where KCl was present in the intra- and extravesicular media, removal of chloride ions from the release solution produced a 2-fold increase in the rate of Ca(2+)-induced Ca2+ release. Together, these results suggest that, besides their involvement in the action potential time course, chloride ions could exert a negative control on the sarcoplasmic reticulum Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)