In frog atrial fibres, cyclopiazonic acid as well as thapsigargin, which are inhibitors of sarcoplasmic reticulum Ca(2+)-ATPase, induced a significant increase in the twitch amplitude without detectable changes in its kinetics. The measurements performed on chemically skinned fibres show that cyclopiazonic acid has no effect on the properties of contractile proteins. In the presence of a T-type Ca2+ channel blocker or L-type Ca2+ channel blocker, cyclopiazonic acid still induced a potentiation of the twitch while no effect was found in the presence of a Na(+)-Ca2+ exchange blocker. The effect of cyclopiazonic acid was not related to any modification in myofibrillar Ca2+ sensitivity or in Ca2+ influx through Ca2+ channels. It is proposed that the inhibition of the sarcoplasmic reticulum Ca(2+)-ATPase resulted in a potentiation of the effect of the Ca2+ influx and that the major role of the sarcoplasmic reticulum was to limit the intracellular Ca2+ concentration.