The functional capacity of skeletal muscle sarcoplasmic reticulum was explored in slow rat soleus muscle after 21 days of hindlimb suspension. The sarcoplasmic reticulum function was assessed in intact and saponin-skinned fibers by using cyclopiazonic acid, a specific Ca(2+)-adenosinetriphosphatase inhibitor. After hindlimb unweighting, the sensitivity to cyclopiazonic acid of intact and skinned soleus fibers becomes similar to that found in fast-twitch muscles. This change could be related to the expression of fast Ca2(+)-adenosinetriphosphatase-pump protein in unloaded soleus muscles and agrees with a transformation of soleus muscle from slow- to fast-twitch type. These results also indicate that specific pharmacological tools, like cyclopiazonic acid, could be used to analyze subcellular functional changes due to hindlimb unweighting.