Binge drinking of alcohol, cocaine overdose, or overexertion can lead to rhabdomyolysis characterized by elevated creatine kinase (CK) and myoglobin in the serum, myoglobinuria, and muscle tenderness. Our previous studies showed that ethanol, cocaine, and electrical stimulation enhanced the leakage of CK from isolated soleus and extensor digitorum longus (EDL) muscles of rat. Dantrolene sodium was reported to reduce the muscle damage and elevated serum CK levels in exercised rats. The present study was aimed at testing whether dantrolene can reduce the enhanced leakage of CK from isolated rat soleus and EDL muscles caused by ethanol, cocaine, and electrical stimulation. After 4-hr incubation in oxygenated physiological solution at 37 degrees C, the mean leakage of CK was 1.56 units/mg of muscle in soleus and 0.89 units/mg in EDL. Ethanol at 0.2% increased the leakage of CK by 47% (p < 0.05) in soleus and by 26% in EDL. Cocaine at 1 mM increased the leakage of CK by 55% (p < 0.05) in soleus and by 27% in EDL. Electrical stimulation at 1 Hz for 4 hr increased the mean leakage of CK by 100% (p < 0.05) in soleus and 127% (p < 0.05) in EDL. Dantrolene sodium reduced the enhanced leakage of CK caused by ethanol, cocaine, and electrical stimulation significantly in soleus and slightly in EDL. Dantrolene may involve myoplasmic free Ca2+ in these beneficial effects as in malignant hyperthermia, and may be useful in the treatment of rhabdomyolysis associated with acute alcoholic myopathy, cocaine overdose, and overexertion.