The effects of halothane (1.9 mM, 9.4 mM), enflurane (3.3 mM, 16.5 mM), and isoflurane (1.6 mM, 8.1 mM) on maximal Ca(2+)-activated force and Ca2+ sensitivity were studied in rat myocardial preparations rendered permeable by various methods. In preparations permeabilized either by mild homogenization or by saponin (50 micrograms/ml, 30 min), further disruption of the sarcolemma with 2% Triton X-100 resulted in increased maximal force and Ca2+ sensitivity. When membranes were mechanically disrupted or saponized, each vapor agent caused the myocardium to be more sensitive to Ca2+. In these preparations, maximal force was decreased by halothane but was not affected by enflurane or isoflurane. With cellular membranes completely disrupted by Triton, the previously observed increase in Ca2+ sensitivity caused by enflurane was reduced, whereas that caused by halothane and isoflurane was abolished and maximal force was decreased by halothane and isoflurane but was not affected by enflurane. These results indicate that 1) components associated with the cellular membrane systems normally modulate force in mammalian myocardium, and 2) halothane, enflurane, and isoflurane have complex effects on these components. These results therefore can explain some of the differences in inotropic effects that these agents exert on mammalian myocardium.