The aim of this study was to investigate if the Na(+)-channel activating alkaloid veratrine is able to change the oxidative and m-ATPase activities of a fast-twitch glycolytic muscle (EDL, extensor digitorum longus) and slow-twitch oxidative muscle (SOL, soleus) in mice. Oxidative fibers and glycolytic fibers were more sensitive to veratrine than oxidative-glycolytic fibers 15, 30 and 60 min after the i.m. injection of veratrine (10 ng/kg) with both showing an increase in their metabolic activity in both muscles. In EDL, the m-ATPase reaction revealed a significant (p < 0.001) decrease (50%) in the number of type IIB fibers after 30 min while the number of type I fibers increased by 550%. Type I fibers decreased from 34% in control SOL to 17% (50% decrease) in veratrinized muscles, with a 10% decrease in type IIA fibers within 15 min. A third type of fiber appeared in SOL veratrinized muscle, which accounted for 28% of the fibers. Our work gives evidence that the changes in the percentage of the fiber types induced by veratrine may be the result, at least partially, from a direct effect of veratrine on muscle fibers and else from an interaction with the muscle type influencing distinctively the response of a same fiber type. Based on the results obtained in the present study the alterations in EDL may be related to the higher number of Na(+) channels present in this muscle whereas those in SOL may involve an action of veratrine on mitochondria. Although it is unlikely that the shift of enzymes activities induced by veratrine involves genotypic expression changes an alternative explanation for the findings cannot be substantiated by the present experimental approach.401471-81