The effects of halothane on caffeine-induced tension transients in functionally skinned myocardial fibers were investigated. Fiber bundles from mechanically disrupted rabbit right ventricular papillary muscles were mounted on a tension transducer. The fiber preparation was loaded with Ca2+; Ca2+ was then released by the use of caffeine (25 mM); and the area of the resulting tension transient was measured. Each preparation was sequentially transferred from control to test to control solution. The control solutions were equilibrated with 100% N2, and the test solutions with a mixture of N2 and various halothane concentrations. The preparation was exposed to halothane during the Ca2+ uptake or the release phase only, or during both Ca2+ uptake and release phases. The areas of the test tension transients were compared with those of the two control tension transients. It was found that halothane depressed the caffeine-induced tension transient either during the uptake phase or the combined-uptake-and-release phase but not during the release phase. The halothane-induced depression was dose-dependent, reversible, and comparable to the depression observed in intact isolated papillary muscles. We conclude that halothane could induce myocardial depression by inhibiting Ca2+ uptake by the sarcoplasmic reticulum.