Contractile and histochemical properties of rat soleus muscle were studied bilaterally after 2 or 4 weeks of denervation (DEN), which eliminates activity and non-activity-related influences, and chronic application of tetrodotoxin (TTX) to the motor nerve, which produces a completely inactive innervated muscle. After 2 or 4 weeks of disuse, the percentages of slow twitch oxidative fibers in both DEN- and TTX- treated soleus were reduced significantly and to similar extents. The dynamic contractile properties of TTX-treated and denervated muscles were similar to those of control muscle after 2 weeks, but by 4 weeks, parallel increases were seen in normalized rate of tension development and maximal shortening speed of these muscles. After either period of disuse, the atrophy of TTX-treated soleus was significantly less than that of denervated muscle. Atrophy was associated with correspondingly diminished capacity of denervated or TTX-disused muscles to generate tension after 2 weeks. By 4 weeks of treatment, the reduction in tension of denervated soleus was greater than its diminished size. These results imply the existence of a non-activity-related stimulus in TTX-inactivated muscles which slows the reductions in muscle mass and specific tension observed in denervated soleus muscle. In contrast, the similarities in dynamic speed-related properties and fiber type profiles between DEN- and TTX-treated rat soleus may be explained simply by the absence of neuromuscular activity.