Exertional rhabdomyolysis is a myopathy of unknown pathophysiology. We measured intracellular resting calcium concentration ([Ca2+]i) by means of Ca(2+)-selective microelectrodes in intercostal muscle fibers from horses suffering from rhabdomyolysis, and from horses with no evidence of neuromuscular disorder. [Ca2+]i was several-fold higher in muscle fibers from horses suffering from rhabdomyolysis when compared to controls. Treatment of rhabdomyolytic horses with dantrolene, an agent that prevents Ca2+ release from the sarcoplasmic reticulum, reduced [Ca2+]i toward control values, and accelerated the recovery from this myopathy. These results indicate that an acute episode of rhabdomyolysis is associated with elevation in [Ca2+]i in skeletal muscles, and that dantrolene might be of benefit in treating this disease.