The effects of various volatile anesthetics on intramuscular Ca2+-related functions were studied with the skinned fiber technique in guinea pig skeletal muscles. All the volatile anesthetics tested significantly enhanced Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR) at clinical concentrations with negligible effects both on Ca2+ sensitivity of the contractile system and on Ca2+ uptake by the SR. A comparison was made of the enhancing effect of several volatile anesthetics on CICR at clinical concentrations. Halothane was the most potent, followed by methoxyflurane, isoflurane, enflurane, sevoflurane and diethyl ether. If CICR plays an important role in triggering MH, this order of volatile anesthetics on their enhancing effect on CICR, also corresponds to their potency in triggering MH.