The effects of halothane or cooling on Ca2+-activated tensions and on the uptake and release of Ca2+by the sarcoplasmic reticulum were investigated in chemically skinned fibers of the extensor digitorum longus muscle of adult rabbits. At 22° C, halothane (>0.46 mM) induced Ca2+release from the SR of Ca2+-loaded skinned fibers that resulted in transient tensions. Higher concentrations of halothane (>4.65 mM) reduced the steady-state accumulation of Ca2+in the SR at 22° C. Cooling (to <10° C) elicited transient contractures (cooling-induced contractures [CC]) in Ca2+-Ioaded skinned fibers, despite the fact that the tensions elicited by adding Ca2+to the bath were depressed at these low temperatures. The skinned fibers did not develop CCs at 12–16° C. Halothane cooling contractures could be elicited at these temperatures by exposing the fibers to halothane concentrations that failed to elicit Ca2+release at 22° C. The halothane cooling contractures were blocked by procaine but not by lidocaine. It was concluded that these contractures resulted from a synergistic interaction between halothane and cooling that stimulates Ca2+release from, and reduces Ca2+uptake by, the sarcoplasmic reticulum.