The effect of cyclopiazonic acid, an inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase, was investigated on force generation by the contractile apparatus in Triton-skinned fibres from extensor digitorum longus and soleus. Concentrations of cyclopiazonic acid lower than 10 microM were without effect on Ca(2+)-activated tension in both types of muscles. In contrast, in soleus, cyclopiazonic acid (20, 50, 100 microM) was found to shift reversibly the relation-tension pCa (-log[Ca2+]) towards lower free Ca2+ and to decrease maximal Ca(2+)-activated tension, in a dose-dependent manner. In extensor digitorum longus, the Ca2+ sensitivity was significantly increased only at a high cyclopiazonic acid concentration (100 microM) and for all the concentrations tested between 5 to 100 microM maximal Ca(2+)-activated tension was unchanged. These results suggest that cyclopiazonic acid has a direct effect on contractile proteins, in a dose-dependent manner. Ca2+ sensitivity and Ca(2+)-activated maximal tension of the contractile apparatus were differentially affected in fast- (extensor digitorum longus) and slow-twitch (soleus) fibres from ferret skeletal muscle.