Mononucleated cells located between the external lamina and sarcolemma of denervated muscle fibers within the extensor digitorum longus (EDL) and soleus muscles of adult mice were quantified and examined ultrastructurally from 3 to 65 days after ligating and removing a section of the sciatic nerve. During the first 2 weeks postdenervation, mononucleated cells in denervated muscles were morphologically indistinguishable from satellite cells observed in control muscles. With time, however, many of these satellite-like cells appeared more active as evidenced by a decrease in their nucleocytoplasmic ratio and an increase in their mean percentage of euchromatin material. The number of satellite cells (expressed as a ratio of satellite cell nuclei to satellite cell nuclei plus myonuclei) did not increase significantly until 30 days postdenervation, at which time the mean percentage for the soleus muscle had risen from a control value of 4.1-8.5%, and for the EDL from 1.2-4.1%. Small-diameter, presumably regenerating, myofibers were occasionally observed but only after 30 days denervation. The ultrastructural evidence plus comparisons of euchromatin distributions between myonuclei and satellite cell nuclei support the concept that an increase in the number of satellite-like cells during denervation is more likely due to satellite cell proliferation than to the formation of mononucleated fragments utilizing preexisting myonuclei.