To assess a possible role for adenosine in muscle cell apoptosis, we have studied the effects of its hydrolysis-resistant analogue 2-chloro adenosine on a myogenic cell line, C2C12, which can differentiate in vitro to giant multinucleated cells (myotubes). Exposure of cultures to the adenosine analogue resulted in time-dependent apoptotic cell death of both myoblasts and myotubes. Adenosine may therefore represent an endogenous regulator of pathophysiological apoptosis in muscle.