To evaluate the hypothesis that maintenance of the integrity of myocardial membrane systems and prevention of Ca2+ influx into the cell are significant in the survival of ischaemic tissue, the effect of trifluoperazine and lysolecithin, were tested on the recovery of globally ischaemic rat hearts. Trifluoperazine increases membrane stabilization, inhibits calmodulin and binds to other Ca2+-dependent proteins. Lysolecithin, on the other hand, has a detergent action on myocardial cell membranes and facilitates Ca2+ ingress in ischaemic tissue. With trifluoperazine (2.45 microM), added before induction of ischaemia or during reperfusion only, hearts subjected to 40 min normothermic ischaemic cardiac arrest recovered mechanically. Untreated hearts failed after 20 min of ischaemia. The drug had no effect on tissue high energy phosphate levels or mitochondrial oxidative phosphorylation. Conversely, lysolecithin (2.5-10 microM) caused all hearts to fail after being subjected to 15 min ischaemia. Mechanical failure during reperfusion of such hearts was associated with a significant reduction in tissue ATP and CrP levels. Trifluoperazine counteracted the harmful effects of lysolecithin to a limited extent.