The aim of the study was to investigate whether Na+ channels play a role in the twitch component of the response of the isolated frog rectus abdominis to Ca2+-free Ringer solution with 0.2 mM Na(2)EDTA by using tetrodotoxin and some other well known drugs that exhibit a blocking action on Na+ channels. In the presence of 5 X 10(-7) M tetrodotoxin, the twitch component, measured isotonically, disappeared. Although 10(-7) M d-tubocurarine was found to be ineffective, a complete blockage of twitch amplitude was observed at 5 x 10(-6) M concentration of the drug. The inhibitory action of d-tubocurarine on twitch response was not antagonized by 10(-6) and 10(-5) M carbachol. Propranolol (10(-6) - 10(-5) M), lidocaine (2 x 10(-6) - 10(-5) M), quinine (10(-6) - 2 X 10(-5) M) and quinidine (10(-6) - 2 X 10(-5) M) inhibited maximal twitch amplitude in a concentration dependent manner. These findings strongly suggest that activation of tetrodotoxin sensitive Na+ channel may play a primary role at twitch generation during exposure of the frog rectus abdominis to Ca2+-free Ringer solution with Na-2 EDTA.